Use of genes PRDX5 and GPX4 in preparation of drug for castration-resistant prostate cancer

Abstract

The present invention relates to the technical field of biomedicine. Disclosed is a use of genes PRDX5 and GPX4 in the preparation of a drug for castration-resistant prostate cancer (CRPC). The present invention proposes that silencing or interfering with the expression of genes PRDX5 and / or GPX4 can be used for treatment or adjuvant treatment of CRPC. The present invention provides, for the first time, a new strategy for using a siRNA in combination with an androgen receptor antagonist to prepare a drug for treating CRPC, and multi-angle and multi-level validation studies are carried out. In the present invention, a pharmaceutical composition in which the siRNA and the androgen receptor inhibitor are combined can be used for treating CRPC and significantly improve the inhibitory effect of Enzalutamide on CRPC, providing a basis for the design and clinical application of nucleic acid drugs, and having important clinical treatment significance.

Description

Application of genes PRDX5 and GPX4 in the preparation of drugs for castration-resistant prostate cancer Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and particularly relates to the application of genes PRDX5 and GPX4 in preparing drugs for castration-resistant prostate cancer. Background Art

[0002] Androgen deprivation therapy (ADA) is the standard treatment for advanced prostate cancer, but patients will eventually progress to castration-resistant prostate cancer (CRPC) after an average of 1-3 years of treatment. CRPC refers to prostate cancer that progresses despite an initial course of continuous ADA (androgen deprivation therapy). Since docetaxel was shown to prolong overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) in 2004, drugs targeting the mCRPC stage, such as abiraterone acetate, enzalutamide, and cabazitaxel, have emerged in recent years, transforming the treatment landscape for these patients. However, these drugs ultimately fail to completely reverse CRPC. Therefore, finding other effective therapeutic targets is another research hotspot for the treatment of CRPC.

[0003] Peroxiredoxin 5 (PRDX5) is the only atypical 2-Cys peroxiredoxin in mammals. It is located in mitochondria, peroxisomes, cytoplasm and nucleus. It is a cell-protective antioxidant enzyme against endogenous or exogenous peroxidation attacks. Studies have shown that PRDX5 is necessary for cancer cells to maintain vitality under oxidative stress (OS) conditions, and overexpression of PRDX5 helps protect cells from OS-induced apoptosis. OS refers to a state of imbalance between oxidation and antioxidant effects in the body. It is the result of an imbalance between the generation of reactive oxygen species (ROS) and antioxidant forces. It can promote pathological defects in organisms, such as cancer and diabetes, and can also damage cellular components, such as DNA. ROS are very active oxygen species, including hydrogen peroxide (H2O2), superoxide anions (O 2- ), hydroxyl radicals, etc., cancer cells express increased levels of ROS; however, antioxidants such as PRDX5 present in cancer cells can detoxify ROS, which promotes the growth and development of cancer cells. When the balance between ROS and antioxidants is disrupted, the intracellular ROS threshold level increases, leading to OS-mediated cell apoptosis.

[0004] Phospholipid hydroperoxide glutathione peroxidase (GPX4) is an essential antioxidant peroxidase that directly reduces phospholipid hydroperoxides, even when they are incorporated into membranes and lipoproteins. It can also reduce fatty acid hydroperoxides, cholesterol hydroperoxides, and thymine hydroperoxides. It plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation. A 2017 Nature report showed that cancer cells in a state of high stromal therapy resistance have selective sensitivity to ferroptosis, a non-apoptotic cell death caused by the iron-dependent accumulation of lipid reactive oxygen species, which can be induced by inhibiting the lipid hydroperoxidase GPX4. The study found that sensitivity to GPX4 inhibition is a general susceptibility of persistent cells.

[0005] Small nucleic acid drugs (siRNAs) exert their efficacy through RNA interference (RNAi), restricting the selection of corresponding targets with high specificity. They can also expand the drug target to upstream RNA of functional proteins, regulating target gene expression at the post-transcriptional level. In the early stages of siRNA therapy development, many drugs were designed based on completely unmodified or slightly modified siRNAs to reach appropriate tissues and then silence the target gene. These molecules can mediate gene silencing in vivo. However, these approaches may be observed to have limited efficacy and potential off-target effects. Therefore, chemically modified siRNAs, such as replacing the 2'-OH group with 2'-O-methyl (2'-OMe) or 2'-methoxyethyl (2'-MOE) groups, can effectively inhibit the innate immune activation driven by immunostimulatory siRNAs, enhance activity and specificity, and reduce off-target toxicity. To improve the efficacy of siRNAs and reduce their potential toxicity, many chemical modifications have been established and tested. The present invention intends to prepare the effective therapeutic targets of CRPC, PRDX5 and GPX4, into modified siRNA drugs with RNA interference effects in cells and mice, so as to reduce the expression of PRDX5, GPX4, and PRDX5+GPX4 and delay the development of CRPC.

[0006] Summary of the Invention

[0007] The technical problem to be solved by the present invention is to find an effective therapeutic target and provide a nucleic acid drug for the effective treatment of CRPC, namely the nucleic acid drug siPRDX5, to achieve a significant improvement in the efficacy of CRPC.

[0008] After extensive research and exploration, the present invention has discovered nucleic acid drugs for the treatment of CRPC, namely siPRDX5 and siGPX4. The results showed that when administered to human prostate cancer LNCaP cells, mouse MyC-CaP cells, and transient drug-tolerant persister (DTP) cells formed by LNCaP and MyC-CaP cells, either siPRDX5 or siGPX4 alone could reduce the expression of PRDX5 or GPX4 in cancer cells, and the combination of siPRDX5 and siGPX4 could simultaneously reduce the expression of PRDX5 and GPX4. Gene expression and protein expression were verified by q-RTPCR and Western Blot assays.

[0009] The present invention applies siPRDX5 or siGPX4 or siPRDX5+siGPX4 to LNCaP / MyC-CaP-DTP and 22Rv1 cells, and verifies the drug effect by CCK8 cell proliferation analysis. The results show that siPRDX5 or siGPX4 or siPRDX5+siGPX4 can significantly inhibit the growth of LNCaP-DTP, MyC-CaP-DTP and 22Rv1 cells. At the same time, a CRPC mouse model is constructed in which C-MYC-overexpressing prostate cancer mice are continuously gavaged with ENZ. CRPC mice are treated with siPRDX5 or siGPX4 or siPRDX5+siGPX4, and the enzyme activity of PRDX5 in the mice is observed to verify the therapeutic effect of the drug on prostate cancer. The results show that siPRDX5 or siGPX4 or siPRDX5+siGPX4 can effectively inhibit the progression of prostate cancer in CRPC mice by inhibiting the enzyme activity of PRDX5.

[0010] The first object of the present invention is to provide a double-stranded siRNA molecule, as shown in any one of the following (A) to (C):

[0011] (A) siRNA molecule siPRDX5 that inhibits PRDX5 gene expression, comprising a double-stranded siRNA molecule formed by complementation of the RNA single strand shown in SEQ ID NO. 1 and the RNA single strand shown in SEQ ID NO. 2;

[0012] (B) siRNA molecule siGPX4 for inhibiting GPX4 gene expression, comprising a double-stranded siRNA molecule formed by complementation between the RNA single strand shown in SEQ ID NO. 3 and the RNA single strand shown in SEQ ID NO. 4, or a double-stranded siRNA molecule formed by complementation between the RNA single strand shown in SEQ ID NO. 5 and the RNA single strand shown in SEQ ID NO. 6;

[0013] (C) A composition comprising (A) and (B).

[0014] In one embodiment of the present invention, at least one nucleotide in the double-stranded siRNA molecule is a modified nucleotide.

[0015] In one embodiment of the present invention, all nucleotides in the double-stranded siRNA molecule are modified nucleotides.

[0016] In one embodiment of the present invention, the modification is selected from phosphorothioate, 2'-F, 2'-OMe, 2'-Ara-F, 2'-O-MO, m 6 A or m 5 At least one of C.

[0017] In one embodiment of the present invention, the modification is as shown in any one of (1) to (7):

[0018] In one embodiment of the present invention, the double-stranded siRNA molecules are as shown in any one of (A1) to (A16), (B1) to (B16), and (C1) to (C16), wherein (A1) to (A16) are double-stranded siRNAs modified for siPRDX5, and (B1) to (B16) and (C1) to (C16) are double-stranded siRNAs modified for siGPX4:

[0019] (A1):

[0020] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0021] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0022] (A2)

[0023] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0024] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0025] (A3)

[0026] 5’(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3’;

[0027] 5’[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3’;

[0028] (A4)

[0029] 5’(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3’;

[0030] 5’[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3’;

[0031] (A5)

[0032] 5’(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0033] 5’[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3’;

[0034] (A6)

[0035] 5’(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3’;

[0036] 5’[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3’;

[0037] (A7)

[0038] 5’(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0039] 5’[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3’;

[0040] (A8)

[0041] 5’(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0042] 5’[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3’;

[0043] (A9)

[0044] 5’(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0045] 5’[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3’;

[0046] (A10)

[0047] 5’(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3’;

[0048] 5’[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3’;

[0049] (A11)

[0050] 5’(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3’;

[0051] 5’[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3’;

[0052] (A12)

[0053] 5’(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3’;

[0054] 5’[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3’;

[0055] (A13)

[0056] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0057] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0058] (A14)

[0059] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0060] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0061] (A15)

[0062] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0063] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0064] (A16)

[0065] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0066] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0067] (B1)

[0068] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0069] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0070] (B2)

[0071] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0072] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0073] (B3)

[0074] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0075] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0076] (B4)

[0077] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0078] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0079] (B5)

[0080] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0081] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0082] (B6)

[0083] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0084] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0085] (B7)

[0086] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0087] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0088] (B8)

[0089] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0090] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0091] (B9)

[0092] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0093] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0094] (B10)

[0095] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0096] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0097] (B11)

[0098] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0099] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0100] (B12)

[0101] 5'(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3';

[0102] 5'[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3';

[0103] (B13)

[0104] 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3';

[0105] 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3';

[0106] (B14)

[0107] 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3';

[0108] 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3';

[0109] (B15)

[0110] 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3';

[0111] 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3';

[0112] (B16)

[0113] 5’(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3’;

[0114] 5’[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3’;

[0115] (C1)

[0116] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0117] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0118] (C2)

[0119] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0120] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0121] (C3)

[0122] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0123] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0124] (C4)

[0125] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0126] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0127] (C5)

[0128] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0129] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0130] (C6)

[0131] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0132] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0133] (C7)

[0134] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0135] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0136] (C8)

[0137] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0138] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0139] (C9)

[0140] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0141] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0142] (C10)

[0143] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0144] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0145] (C11)

[0146] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0147] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0148] (C12)

[0149] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0150] 5'[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3';

[0151] (Q13)

[0152] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0153] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3';

[0154] (C14)

[0155] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0156] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3';

[0157] (C15)

[0158] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0159] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3';

[0160] (C16)

[0161] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0162] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3';

[0163] Wherein, A-, U-, C-, and G- represent phosphorothioate-modified ribonucleotides A, U, C, and G, respectively;

[0164] (A), (U), (C), and (G) represent 2′-F-modified ribonucleotides A, U, C, and G, respectively;

[0165] [A], [U], [C], and [G] represent 2′-OMe-modified ribonucleotides A, U, C, and G, respectively;

[0166] (A), (U), (C), and (G) represent ribonucleotides A, U, C, and G modified with 2′-Ara-F, respectively;

[0167] [A], [U], [C], and [G] represent 2′-O-MOE-modified ribonucleotides A, U, C, and G, respectively;

[0168] A*, U*, C* and G* represent the m 6 A-modified ribonucleotides A, U, C, and G;

[0169] A', U', C' and G' respectively represent the 5 C-modified ribonucleotides A, U, C, and G.

[0170] The second object of the present invention is to provide a biological material related to the siRNA, which is any of the following:

[0171] (1) a vector for expressing the siRNA;

[0172] (2) a host cell carrying the siRNA or the vector;

[0173] (3) a reagent containing the siRNA, or (1) the vector, or (2) the host cell;

[0174] (4) A pharmaceutical composition containing the siRNA.

[0175] In one embodiment of the present invention, the pharmaceutical composition may further contain androgen or androgen receptor inhibitor.

[0176] In one embodiment of the present invention, the androgen receptor inhibitor is selected from Enzalutamide (ENZ).

[0177] In one embodiment of the present invention, the pharmaceutical composition contains a pharmaceutically acceptable carrier or excipient.

[0178] In one embodiment of the present invention, the pharmaceutically acceptable carrier comprises liposomes, micelles, metal particles, or polymer particles.

[0179] The third object of the present invention is to provide the use of the siRNA or the biomaterial in preparing a drug for preventing or treating prostate cancer.

[0180] In one embodiment of the present invention, the prostate cancer is advanced prostate cancer or castration-resistant prostate cancer.

[0181] The fourth object of the present invention is to provide a method for preventing or treating prostate cancer, comprising administering the siRNA or the biomaterial to a subject.

[0182] A fifth object of the present invention is to provide a method for inhibiting the expression of PRDX5 and / or GPX4 genes in cells, characterized in that the method comprises contacting an effective amount of the siRNA or the biomaterial with cells, thereby inhibiting the expression of PRDX5 and / or GPX4 genes in cells. Beneficial effects:

[0183] 1. The present invention proposes for the first time that interfering with or silencing the expression of genes PRDX5 and / or GPX4 can improve prostate cancer, especially castration-resistant prostate cancer. It has a significant killing effect on castration-resistant prostate cancer cells, with a cell inhibition rate of about 50%. It also reduces the prostate weight of drug-resistant CRPC mice and inhibits tumor growth. After combined use with the androgen receptor inhibitor ENZ, the prostate weight can be reduced to about 40 mg. It also significantly inhibits the activity of PRDX5 enzyme in the prostate.

[0184] 2. This invention, for the first time, proposes a method for preparing a CRPC treatment drug using the nucleic acid drugs siPRDX5 and / or siPGX4. This will significantly advance the application of nucleic acid drugs in the clinical treatment of prostate cancer. Drug research, on average, takes 8-10 years from molecular compound development to clinical application, requiring significant human and material resources, resulting in significant time and financial costs. The present invention's approach can significantly shorten the timeline from drug discovery to clinical translation. BRIEF DESCRIPTION OF THE DRAWINGS

[0185] Figure 1 shows the mRNA expression levels of PRDX5 and GPX4 detected by qRT-PCR in LNCaP and LNCaP-derived DTP cells (LNCaP-DTP) after the addition of the first, second, and third siPRDX5 and the first, second, third, and fourth siGPX4 siRNAs provided by the present invention; wherein, Figure A is the relative expression level of PRDX5 in LNCaP cells; Figure B is the relative expression level of PRDX5 in LNCaP-DTP cells; Figure C is the relative expression level of GPX4 in LNCaP cells; and Figure D is the relative expression level of GPX4 in LNCaP-DTP cells.

[0186] Figure 2 shows the mRNA expression level of PRDX5 detected by qRT-PCR in LNCaP, MyC-CaP cells, and LNCaP-derived DTP cells LNCaP-DTP and MyC-CaP-derived DTP cells (MyC-CaP-DTP) after the addition of the modified third siPRDX5 provided by the present invention; wherein, Figure A is LNCaP cells; Figure B is MyC-CaP cells; Figure C is LNCaP-DTP cells; and Figure D is MyC-CaP-DTP cells.

[0187] Figure 3 is the mRNA expression level of GPX4 detected by qRT-PCR in LNCaP, MyC-CaP cells, LNCaP-derived DTP cells (LNCaP-DTP), and MyC-CaP-derived DTP cells (MyC-CaP-DTP) after the addition of the third and fourth modified siGPX4 provided by the present invention; wherein, Figure A is LNCaP cells; Figure B is MyC-CaP cells; Figure C is LNCaP-DTP cells; and Figure D is MyC-CaP-DTP cells.

[0188] Figure 4 shows the expression changes of PRDX5 or GPX4 proteins detected by WB after the addition of unmodified third siPRDX5 or siGPX4 to LNCaP and MyC-CaP cells; wherein, Figure A is the detection of PRDX5 protein expression in LNCaP cells; Figure B is the detection of PRDX5 protein expression in MyC-CaP cells; Figure C is the detection of GPX4 protein expression in LNCaP cells; Figure D is the detection of GPX4 protein expression in MyC-CaP cells.

[0189] Figure 5 shows the cell viability detected by CCK8 after adding the modified third siPRDX5-1-16 or the modified third siGPX4-1-16 or the modified third siPRDX5-1-16+modified third siGPX4-1-16 to LNCaP-DTP and MyC-CaP-DTP cells; Figure A shows the effect of adding siPRDX5-1-16 on the viability of LNCaP-DTP cells; Figure B shows the effect of adding siPRDX5-1-16 on the viability of MyC-CaP-DTP cells; Figure C shows the effect of adding siPRDX5-1-16 on the viability of 22Rv1 cells; Figure D shows the effect of adding siGP Figure E shows the effect of adding siGPX4-1-16 on the survival rate of LNCaP-DTP cells; Figure F shows the effect of adding siGPX4-1-16 on the survival rate of 22Rv1 cells; Figure G shows the effect of adding siPRDX5-1-16+siGPX4-1-16 on the survival rate of LNCaP-DTP cells; Figure H shows the effect of adding siPRDX5-1-16+siGPX4-1-16 on the survival rate of MyC-CaP-DTP cells; Figure I shows the effect of adding siPRDX5-1-16+siGPX4-1-16 on the survival rate of 22Rv1 cells.

[0190] Figure 6 is a graph showing the effects of the NC control group, ENZ, the third siPRDX5-1, the third siPRDX5-16, the third siGPX4-1, the third siGPX4-16, the third siPRDX5-16+the third siGPX4-16, and their combination with ENZ on the prostate weight changes in C-MYC overexpressing prostate cancer mice after continuous ENZ administration to produce CRPC; Figure A is a graph showing the weight changes of mice in each group (NC, ENZ, siPRDX5-1, ENZ+siPRDX5-1 group) following drug administration; Figure B is a comparison graph of the prostates of 8-month-old mice in each group taken for photographing; Figure C is a graph showing the prostate weight changes of 8-month-old mice in each group.

[0191] Figure 7 is a graph showing the changes in PRDX5 protease activity in C-MYC overexpressing prostate cancer mice treated with NC control group, ENZ, the third siPRDX5-1, the third siPRDX5-16, the third siGPX4-1, the third siGPX4-16, the third siPRDX5-16+the third siGPX4-16, and the combination of ENZ and the NC control group after continuous treatment with ENZ to produce CRPC; Figure A is a HE staining image of prostate tissue sections of 8-month-old mice in each group; Figure B is a quantitative graph of PRDX5 enzyme activity in the prostate tissues of mice in each group. DETAILED DESCRIPTION

[0192] The present invention will be further described below with reference to the accompanying drawings and specific examples, but the examples do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0193] Unless otherwise specified, the reagents and materials used in the following examples were commercially available.

[0194] Example 1 Synthesis of unmodified siRNA

[0195] siRNAs were designed based on the full mRNA sequences of human PRDX5 and GPX4. The activity of all candidate siRNAs was evaluated using basic siRNA design principles, and preliminary siRNA designs and synthesis were performed. All sequences were obtained from the NCBI gene database.

[0196] (1) The siPRDX5 sequence is:

[0197] The first one:

[0198] 5'-AGACAGACUUAUUACUAGAUGAUTC-3' (SEQ ID NO. 7);

[0199] 5'-GAAUCAUCUAGUAAUAAGUCUGUCUCC-3' (SEQ ID NO. 8);

[0200] The second type:

[0201] 5'GGCCAGAUUUCUGCAAUAAACACTT-3' (SEQ ID NO.9);

[0202] 5'AAGUGUUUAUUGCAGAAAUCUGGCCAA-3' (SEQ ID NO. 10);

[0203] The third type:

[0204] 5'-CAGACUUAUUACUAGAUGAUT-3' (SEQ ID NO. 1);

[0205] 5'-AAUCAUCUAGUAAUAAGUCUGUC-3' (SEQ ID NO. 2);

[0206] (2) The siGPX4 sequence is:

[0207] The first one:

[0208] 5'-GUGAGGCAAGACCGAAGUAAACUAC-3' (SEQ ID NO. 11);

[0209] 5'-GUAGUUUACUUCGGUCUUGCCUCACUG-3' (SEQ ID NO. 12);

[0210] The second type:

[0211] 5'-CUACAACGUCAAAUUCGAUAUGUTC-3' (SEQ ID NO. 13);

[0212] 5'-GAACAUAUCGAAUUUGACGUUGUAGCC-3' (SEQ ID NO. 14);

[0213] The third type:

[0214] 5'-ACAACGUCAAAUUCGAUAUGU-3' (SEQ ID NO.3);

[0215] 5'-ACAUAUCGAAUUUGACGUUGUAC-3' (SEQ ID NO.4);

[0216] The fourth type:

[0217] 5'-GUGAGGCAAGACCGAAGUAAA-3' (SEQ ID NO. 5);

[0218] 5'-UUUACUUCGGUCUUGCCUCACUG-3'(SEQ ID NO.6);

[0219] Example 2 Gene interference ability of unmodified siPRDX5 and siGPX4 on prostate cancer cells and DTP cells

[0220] In order to screen suitable siRNAs, the interference activity of the siRNAs designed in Example 1 was tested.

[0221] S1. LNCaP and MyC-CaP cells were cultured at a rate of 1×10 6 The cells were seeded individually in 10 cm cell culture dishes. After adherence on the second day, 50 μM enzalutamide (ENZ) was added and treated for 9 days. During this period, fresh drug-containing culture medium (1640 medium containing 50 μM ENZ) was replaced every three days for culture. The cells were collected and the cells after 9 days of treatment were drug-resistant cells (DTP cells), which were designated as LNCaP-DTP cells and MyC-CaP-DTP cells, respectively.

[0222] S2. LNCaP, MyC-CaP cells and LNCaP-DTP, MyC-CaP-DTP cells collected in S1 were seeded into 6 cm dishes and 10 cm dishes containing fresh complete culture medium (1640 culture medium containing 10% fetal bovine serum and 1% double antibody). After adherence, they were transfected with siPRDX5 and siGPX4 designed in Example 1, and then mRNA and protein were extracted.

[0223] S3. Through qRT-PCR and Western Blot experiments, siRNA with interference activity was screened and verified at the RNA and protein levels.

[0224] The results are shown in Figures 1 and 4 and Tables 1 and 2. The addition of the third siRNA of siPRDX5 successfully and significantly reduced the expression of PRDX5, including the mRNA level and protein level; the addition of the third and fourth siRNAs of siGPX4 successfully and significantly reduced the expression of GPX4, including the mRNA level and protein level. For human prostate cancer cells LNCaP and drug-resistant LNCaP-DTP cells, the mRNA expression level of PRDX5 was reduced to about 0.16 after the third siRNA interference of siPRDX5, while the mRNA expression level of PRDX5 was only reduced to about 0.60 after the first and second siRNA interference of siPRDX5; for human prostate cancer cells LNCaP and drug-resistant LNCaP-DTP cells, the mRNA expression level of GPX4 was reduced to about 0.21 after the third siRNA interference of siGPX4, the mRNA expression level of GPX4 was reduced to about 0.24 after the fourth siRNA interference of siGPX4, while the mRNA expression level of GPX4 was only reduced to about 0.73 after the first and second siRNA interference of siGPX4.

[0225] This shows that the siRNAs designed in Example 1 of the present invention all have the ability to interfere with the expression of target genes to a certain extent, but among them, the third siRNA of siPRDX5 and the third and fourth siRNAs of siGPX4 have better ability to interfere with gene expression.

[0226] Example 3 Modification of siRNA and Verification of Interference Ability

[0227] The third siRNA of siPRDX5, the third siRNA of siGPX4 and the fourth siRNA of siGPX4 obtained by screening in Example 2 were base-modified and synthesized at a biological company, wherein:

[0228] A-, U-, C-, and G- represent phosphorothioate-modified ribonucleotides A, U, C, and G, respectively;

[0229] (A), (U), (C), and (G) represent 2′-F-modified ribonucleotides A, U, C, and G, respectively;

[0230] [A], [U], [C], and [G] represent 2′-OMe-modified ribonucleotides A, U, C, and G, respectively;

[0231] (A), (U), (C), and (G) represent ribonucleotides A, U, C, and G modified with 2′-Ara-F, respectively;

[0232] [A], [U], [C], and [G] represent 2′-O-MOE-modified ribonucleotides A, U, C, and G, respectively;

[0233] A*, U*, C* and G* represent the m 6 A-modified ribonucleotides A, U, C, and G;

[0234] A', U', C' and G' respectively represent the 5 C-modified ribonucleotides A, U, C, and G;

[0235] The base-modified sequences of the third siRNA for siPRDX5 are shown below: siPRDX5-1 to siPRDX5-16:

[0236] siPRDX5-1

[0237] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0238] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0239] siPRDX5-2

[0240] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0241] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0242] siPRDX5-3

[0243] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0244] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0245] siPRDX5-4

[0246] 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3';

[0247] 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3';

[0248] siPRDX5-5

[0249] 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0250] 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3';

[0251] siPRDX5-6

[0252] 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3';

[0253] 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3';

[0254] siPRDX5-7

[0255] 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0256] 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3';

[0257] siPRDX5-8

[0258] 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0259] 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3';

[0260] siPRDX5-9

[0261] 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0262] 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3';

[0263] siPRDX5-10

[0264] 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3';

[0265] 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3';

[0266] siPRDX5-11

[0267] 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3';

[0268] 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3';

[0269] siPRDX5-12

[0270] 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3';

[0271] 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3';

[0272] siPRDX5-13

[0273] 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0274] 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3';

[0275] siPRDX5-14

[0276] 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3';

[0277] 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3';

[0278] siPRDX5-15

[0279] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0280] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0281] siPRDX5-16

[0282] 5’(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3’;

[0283] 5’[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3’;

[0284] The sequences of the third siRNA of siGPX4 with base modifications are shown as siGPX4-1 to siGPX4-16:

[0285] siGPX4-1

[0286] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0287] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0288] siGPX4-2

[0289] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0290] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0291] siGPX4-3

[0292] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0293] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0294] siGPX4-4

[0295] 5’(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3’;

[0296] 5’[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3’;

[0297] siGPX4-5

[0298] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0299] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0300] siGPX4-6

[0301] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0302] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0303] siGPX4-7

[0304] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0305] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0306] siGPX4-8

[0307] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0308] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0309] siGPX4-9

[0310] 5’(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3’;

[0311] 5’[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3’;

[0312] siGPX4-10

[0313] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0314] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0315] siGPX4-11

[0316] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0317] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0318] siGPX4-12

[0319] 5’(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3’;

[0320] 5’[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3’;

[0321] siGPX4-13

[0322] 5’(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3’;

[0323] 5’[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3’;

[0324] siGPX4-14

[0325] 5’(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3’;

[0326] 5’[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3’;

[0327] siGPX4-15

[0328] 5’(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3’;

[0329] 5’[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3’;

[0330] siGPX4-16

[0331] 5’(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3’;

[0332] 5’[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3’;

[0333] The sequences with base modifications for the fourth siRNA of siGPX4 are shown as siGPX4-(1) to siGPX4-(16):

[0334] siGPX4-(1)

[0335] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0336] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0337] siGPX4-(2)

[0338] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0339] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0340] siGPX4-(3)

[0341] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0342] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0343] siGPX4-(4)

[0344] 5’(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3’;

[0345] 5’[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3’;

[0346] siGPX4-(5)

[0347] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0348] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0349] siGPX4-(6)

[0350] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0351] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0352] siGPX4-(7)

[0353] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0354] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0355] siGPX4-(8)

[0356] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0357] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0358] siGPX4-(9)

[0359] 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0360] 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’;

[0361] siGPX4-(10)

[0362] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0363] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0364] siGPX4-(11)

[0365] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0366] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0367] siGPX4-(12)

[0368] 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’;

[0369] 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’;

[0370] siGPX4-(13)

[0371] 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0372] 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’;

[0373] siGPX4-(14)

[0374] 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’;

[0375] 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’;

[0376] siGPX4-(15)

[0377] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0378] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3';

[0379] siGPX4-(16)

[0380] 5'(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3';

[0381] 5'[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3'.

[0382] The results are shown in Figures 2 and 3 and Tables 1 and 2. The same method as in Example 2 was used to treat LNCaP, MyC-CaP cells and their derived LNCaP-DTP, MyC-CaP-DTP cells with the modified siRNA. The results summarized in Tables 1 and 2 show that the third siRNA base-modified sequences siPRDX5-1 to siPRDX5-16 for siPRDX5, the third siRNA base-modified sequences siGPX4-1 to 1-siGPX4-16 for siGPX4, and the fourth siRNA base-modified sequences siGPX4-(1) to the fourth siGPX4-(16) for siGPX4 all had strong interference activity against drug-resistant or non-resistant LNCaP cells and MyC-CaP cells, and the third siGPX4 had a stronger interference efficiency than the fourth siGPX4. It was also found that the interference efficiency against human cells was stronger than that against mouse cells.

[0383] Table 1 Relative expression levels of PRDX5 gene in different cell types after addition of siPRDX5

[0384] Table 2 Relative expression levels of GPX4 gene in different cell types after addition of siGPX4

[0385] Example 4 Killing ability of siPRDX5 and siGPX4 on transient drug-resistant prostate cancer cells

[0386] The CCK8 method was further used to transfect the modified third siPRDX5-1 to 16 or the third siGPX4-1 to 16 or the third siPRDX5-1-16 + the third siGPX4-1-16 synthesized in Example 3 into drug-resistant LNCaP-DTP and MyC-CaP-DTP cells, as well as 22Rv1 cells that are inherently resistant to ENZ, to demonstrate the in vitro anti-tumor effect of nucleic acid drugs in drug-resistant cells.

[0387] 1. Experimental methods

[0388] The drug-resistant cells LNCaP-DTP, MyC-CaP-DTP and ENZ-resistant 22Rv1 cells were seeded into 96-well plates containing fresh 1640 medium. After adherence, 1 to 16 siPRDX5, siGPX4, siPRDX5+siGPX4 and negative control si-neg were added. After successful interference, the transfection mixture was aspirated and replaced with normal complete medium (1640 medium containing 10% fetal bovine serum and 1% double antibody). The cells were cultured in the incubator for 24 hours and finally detected by CCK8. The OD values ​​were calculated. 450 The cell viability was calculated.

[0389] 2. The results are shown in Figure 5. Figure 5A is a bar graph showing the relative survival rates of human prostate cancer resistant cells LNCaP-DTP after treatment with 1 to 16 modified siRNAs of siPRDX5; Figure 5B is a bar graph showing the relative survival rates of mouse prostate cancer resistant cells MyC-CaP-DTP after treatment with siPRDX5-1 to 16 siRNAs; Figure 5C is a bar graph showing the relative survival rates of human prostate cancer resistant ENZ drug cells 22Rv1 after treatment with siPRDX5-1 to 16 siRNAs; Figure 5D is a bar graph showing the relative survival rates of human prostate cancer resistant cells LNCaP-DTP after treatment with siGPX4-1 to 16 siRNAs; Figure 5E is a bar graph showing the relative survival rates of mouse prostate cancer resistant cells MyC-CaP-DTP after treatment with siGPX4-1 to 16 siRNAs. Figure 5F is a bar graph of the relative survival rates of human prostate cancer ENZ drug-resistant cells 22Rv1 after treatment with siGPX4-1 to 16 siRNAs respectively; Figure 5G is a bar graph of the relative survival rates of human prostate cancer resistant cells LNCaP-DTP after treatment with siGPX4-1 to 16 siRNAs and siPRDX5-1 to 16 siRNAs in combination one by one; Figure 5H is a bar graph of the relative survival rates of mouse prostate cancer resistant cells MyC-CaP-DTP after treatment with siGPX4-1 to 16 siRNAs and siPRDX5-1 to 16 siRNAs in combination one by one; Figure 5I is a bar graph of the relative survival rates of human prostate cancer ENZ drug-resistant cells 22Rv1 after treatment with siGPX4-1 to 16 siRNAs and siPRDX5-1 to 16 siRNAs in combination one by one.

[0390] The results showed that in drug-resistant DTP cells generated by continuous ENZ administration for 9 days, continued ENZ treatment had no significant inhibitory effect. However, the addition of nucleic acid drugs, siPRDX5 or siGPX4, with different sequences, achieved approximately 50% inhibition in all three cell lines. Furthermore, the combined effect of siPRDX5 and siGPX4 on all three cell lines was even stronger than that of either siRNA alone. This suggests that siPRDX5 and siGPX4 have a significant killing effect on drug-resistant prostate cancer cells, inhibiting their growth, and the combined effect is even more potent.

[0391] Example 5 Effect of ENZ combined with nucleic acid drugs on C-MYC overexpression prostate cancer mouse model after continuous ENZ administration to generate resistance CRPC

[0392] The results further demonstrated the effects of combined administration of ENZ and a third modified siPRDX5 and a third modified siGPX4 in a mouse model of prostate cancer, in mice that relapsed after chemical castration (i.e., continuous administration of ENZ).

[0393] 1. Experimental methods

[0394] A mouse model of spontaneous prostate cancer with overexpression of C-MYC (Hi-Myc) was constructed. At 4 months of age, mice developed mPIN / cancer transition and were randomly divided into an NC control group (oral administration of solvent) and an ENZ-treated group. The ENZ-treated group received 10 mg / kg of ENZ via oral administration every three days for 30 days. Subsequently, some mice were dissected and their prostate cancers were removed for imaging and weighing. ENZ significantly alleviated symptoms, with prostate weight reduced by half compared to the NC control group. The remaining mice were treated with the same regimen for 60 days, but recurrence of the disease was observed in the ENZ-treated group, successfully generating CRPC mice. Afterwards (i.e., mice were 7 months old), they were randomly divided into: NC control group (always gavaged with solvent), ENZ single-drug group, siPRDX5-1 nucleic acid drug group, ENZ and siPRDX5-1 combination drug group, siPRDX5-16 nucleic acid drug group, ENZ and siPRDX5-16 combination drug group, siGPX4-1 nucleic acid drug group, ENZ and siGPX4-1 combination drug group, siGPX4-16 nucleic acid drug group, ENZ and siGPX4-16 combination drug group, siPRDX5-16+siGPX4-16 nucleic acid drug group, ENZ and siPRDX5-16+siGPX4-16 combination drug group, and corresponding drug treatments were performed. Except for NC and ENZ, which were still gavaged, siPRDX5-1, siPRDX5-16 and siGPX4-1, siGPX4-16 was administered via tail vein injection every three days, maintaining ENZ at 10 mg / kg and siPRDX5-1 / 16 and siGPX4-1 / 16 at 100 nM for a total of 30 days. The mice were then dislocated by cervical dislocation, and prostate cancer cells were removed for imaging, weighing, and HE staining.

[0395] 2. The results are shown in Figures 6 and 7. In Figure 6, Figure 6A shows the changes in body weight of mice in each group as drug administration progresses; Figure 6B shows comparative photographs of the excised prostates of mice in each group; and Figure 6C shows the changes in prostate weight of mice in each group as drug administration progresses. * indicates whether the prostate weight reduction in the other ENZ groups and the siPRDX5 and siGPX4 treatment groups is significant relative to the NC group. In Figure 7, Figure 7A shows HE staining of prostate tissue sections from mice in each group; Figure 7B shows a bar graph of the relative changes in PRDX5 enzyme activity in prostate tissue from mice in each group. * indicates whether the PRDX5 enzyme activity reduction in the other siPRDX5 and siGPX4 treatment groups is significant relative to the ENZ group.

[0396] The results of single and combined use are shown in Table 3:

[0397] Table 3 Effects of different drug administration (30 days) on drug resistance recurrence

[0398] Combining Figure 6 and Table 3, we can see that after 30 days of oral administration of ENZ, the average prostate weight of drug-resistant CRPC mice was 66.67 mg, while the average of the NC control group was 115.6 mg. At this time, the prostate weight of the siPRDX5-1 group, which had been treated for 30 days, had dropped to 53.99 mg, and the prostate weight of the siPRDX5-1 combined with ENZ group had dropped to 49.95 mg, indicating that the siPRDX5 nucleic acid drug has the efficacy of inhibiting tumor growth in CRPC mice. The prostate weight of the siGPX4-1 group, which had been treated for 30 days, was 57.81 mg, and the prostate weight of the siGPX4-1 combined with ENZ group was 49.40 mg, indicating that the siGPX4 nucleic acid drug also has the efficacy of inhibiting tumor growth in CRPC mice. After 30 days of medication, the prostate weight of the siPRDX5-16+siGPX4-16 group decreased to 47.28 mg, and the prostate weight of the siPRDX5-16+siGPX4-16 combined with ENZ group decreased to 39.35 mg, indicating that the efficacy of siPRDX5+siGPX4 nucleic acid drug is more significant.

[0399] The combination of ENZ and siPRDX5 or siGPX4 demonstrated superior efficacy compared to siPRDX5 or siGPX4 alone, reducing prostate weight to approximately 50 mg. Furthermore, siPRDX5 or siGPX4 alone was more effective than ENZ alone after drug resistance, indicating that siPRDX5 or siGPX4 alone has an inhibitory effect on drug-resistant CRPC mice. ENZ combined with both nucleic acid drugs demonstrated the best efficacy, reducing prostate weight to approximately 40 mg.

[0400] PRDX5 enzyme activity was measured using a thioredoxin system. Specifically, the degradation rate of H2O2 was measured by detecting the decrease in A340 caused by NADPH oxidation. The experiment was performed in a 150 μL reaction mixture containing 50 mM HEPES-NaOH (pH 7), 200 μM NADPH, 760 nM mouse TXNRD1, 11 μM human TRX, and varying concentrations of PRDX5. The cells were incubated at 37°C for 5 minutes, and the reaction was initiated by adding 500 μM H2O2.

[0401] The results of PRDX5 enzyme activity in the prostate of different groups are shown in Table 4:

[0402] Table 4 Effects of different drug administration (30 days) on PRDX5 enzyme activity in prostate

[0403] From the results of HE staining of tissue sections (Figure 7), it can be seen that after combined use, CRPC prostate tumors showed significant killing, degradation and fibrosis. Combined with the results of PRDX5 enzyme activity detection in the prostate of different groups (Table 4), it can be seen that when ENZ is continuously gavaged and mice develop CRPC, their PRDX5 enzyme activity increases significantly, reaching a relative value of 4.56. After the use of nucleic acid drug siPRDX5-1, the enzyme activity can be significantly inhibited, reaching a relative value of 2.025, especially when used in combination, it can reach a relative value of 1.465. After the use of nucleic acid drug siGPX4-1, the enzyme activity of PRDX5 can also be significantly inhibited, reaching a relative value of 1.810, and when used in combination, it can reach a relative value of 1.600. It proves that the two nucleic acid drugs have a significant interference effect when used alone. When the two nucleic acid drugs were administered simultaneously, the relative enzyme activity value of PRDX5 in the siPRDX5-16+siGPX4-16 group reached 1.350. When combined with ENZ, the enzyme activity reached the lowest level of 0.955, indicating that the co-administration of siPRDX5-16+siGPX4-16 nucleic acid drugs can achieve the best inhibition of PRDX5 enzyme activity and the best effect of inhibiting prostate tumor growth in CRPC mice.

[0404] Although the present invention has been disclosed above in terms of preferred embodiments, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A double-stranded siRNA molecule, characterized in that As shown in any of the following (A) to (C): (A) An siRNA molecule for inhibiting PRDX5 gene expression, comprising a double-stranded siRNA molecule formed by complementation of a single-stranded RNA as shown in SEQ ID NO.1 and a single-stranded RNA as shown in SEQ ID NO.2; (B) a siRNA molecule for inhibiting the expression of the GPX4 gene, comprising a double-stranded siRNA molecule formed by the complementarity of the RNA single strand shown in SEQ ID NO.3 and the RNA single strand shown in SEQ ID NO.4, or a double-stranded siRNA molecule formed by the complementarity of the RNA single strand shown in SEQ ID NO.5 and the RNA single strand shown in SEQ ID NO.6; (C) A composition comprising (A) and (B).

2. The double-stranded siRNA molecule according to claim 1, characterized in that At least one nucleotide in the double-stranded siRNA molecule is a modified nucleotide.

3. The double-stranded siRNA molecule according to claim 1 or 2, characterized in that All nucleotides in the double-stranded siRNA molecule are modified nucleotides.

4. The double-stranded siRNA molecule according to claim 2 or 3, characterized in that The modification is selected from phosphorothioate, 2'-F, 2'-OMe, 2'-Ara-F, 2'-O-MO, m 6 A or m 5 At least one of C.

5. The double-stranded siRNA molecule according to any one of claims 2 to 4, characterized in that The double-stranded siRNA molecule is as shown in any one of (A1) to (C16): (A1) 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3'; (A2) 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3'; (A3) 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3'; (A4) 5'(C)-[A]-(G)[A](C)[U](U)[A](UUA)[C](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C)[A](U)[C](U)[A](G)[UAA](U)[A](A)[G](U)[C](U)[G]-[U]-[C]3'; (A5) 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3'; (A6) 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3'; (A7) 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3'; (A8) 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3'; (A9) 5'(C)-[A*]-(G)[A*](C)[U](U)[A*](UUA*)[C](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C)[A*](U)[C](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C](U)[G]-[U]-[C]3'; (A10) 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3'; (A11) 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3'; (A12) 5'(C')-[A]-(G)[A](C')[U](U)[A](UUA)[C'](U)[A](G)[A](U)[G](A)[U](T)3'; 5'[A]-(A)-[U](C')[A](U)[C'](U)[A](G)[UAA](U)[A](A)[G](U)[C'](U)[G]-[U]-[C']3'; (A13) 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3'; (A14) 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3'; (A15) 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3'; (A16) 5'(C')-[A*]-(G)[A*](C')[U](U)[A*](UUA*)[C'](U)[A*](G)[A*](U)[G](A*)[U](T)3'; 5'[A*]-(A*)-[U](C')[A*](U)[C'](U)[A*](G)[UA*A*](U)[A*](A*)[G](U)[C'](U)[G]-[U]-[C']3'; (B1) 5'(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3'; (B2) 5'(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3'; (B3) 5'(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3'; (B4) 5'(A)-[C]-(A)[A](C)[G](U)[C](AAA)[U](U)[C](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C)-[A](U)[A](U)[C](G)[A](A)[UUU](G)[A](C)[G](U)[U](G)[U]-[A]-[C]3'; (B5) 5'(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3'; (B6) 5'(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3'; (B7) 5'(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3'; (B8) 5'(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3'; (B9) 5'(A*)-[C]-(A*)[A*](C)[G](U)[C](A*A*A*)[U](U)[C](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C)-[A*](U)[A*](U)[C](G)[A*](A*)[UUU](G)[A*](C)[G](U)[U](G)[U]-[A*]-[C]3'; (B10) 5'(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3'; (B11) 5'(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3'; (B12) 5'(A)-[C']-(A)[A](C')[G](U)[C'](AAA)[U](U)[C'](G)[A](U)[A](U)[G](U)3'; 5'[A]-(C')-[A](U)[A](U)[C'](G)[A](A)[UUU](G)[A](C')[G](U)[U](G)[U]-[A]-[C']3'; (B13) 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3'; (B14) 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3'; (B15) 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3'; (B16) 5'(A*)-[C']-(A*)[A*](C')[G](U)[C'](A*A*A*)[U](U)[C'](G)[A*](U)[A*](U)[G](U)3'; 5'[A*]-(C')-[A*](U)[A*](U)[C'](G)[A*](A*)[UUU](G)[A*](C')[G](U)[U](G)[U]-[A*]-[C']3'; (C1) 5'(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3'; 5'[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3'; (C2) 5'(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3'; 5'[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3'; (C3) 5'(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3'; 5'[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3'; (C4) 5'(G)-[U]-(G)[A](G)[G](C)[A](AGA)[C](C)[G](A)[A](G)[U](A)[A](A)3'; 5'[U]-(U)-[U](A)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A)[C]-[U]-[G]3'; (C5) 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’; (C6) 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’; 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’; (C7) 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’; (C8) 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’; (C9) 5’(G)-[U]-(G)[A*](G)[G](C)[A*](A*GA*)[C](C)[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C](U)[U](C)[G](G)[UCU](U)[G](C)[C](U)[C](A*)[C]-[U]-[G]3’; (C10) 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’; 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’; (C11) 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’; 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’; (C12) 5’(G)-[U]-(G)[A](G)[G](C')[A](AGA)[C'](C')[G](A)[A](G)[U](A)[A](A)3’; 5’[U]-(U)-[U](A)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A)[C']-[U]-[G]3’; (C13) 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’; (C14) 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’; (C15) 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’; (C16) 5’(G)-[U]-(G)[A*](G)[G](C')[A*](A*GA*)[C'](C')[G](A*)[A*](G)[U](A*)[A*](A*)3’; 5’[U]-(U)-[U](A*)[C'](U)[U](C')[G](G)[UC'U](U)[G](C')[C'](U)[C'](A*)[C']-[U]-[G]3’; Among them, A-, U-, C-, and G- respectively represent ribonucleotides A, U, C, and G modified by phosphorothioate; (A), (U), (C), and (G) respectively represent ribonucleotides A, U, C, and G modified by 2’-F; [A], [U], [C], and [G] represent 2′-OMe-modified ribonucleotides A, U, C, and G, respectively; (A), (U), (C), and (G) represent ribonucleotides A, U, C, and G modified with 2′-Ara-F, respectively; [A], [U], [C], and [G] represent 2′-O-MOE-modified ribonucleotides A, U, C, and G, respectively; A*, U*, C* and G* represent the 6 A modified ribonucleotides A, U, C, and G; A', U', C' and G' respectively represent the 5 C-modified ribonucleotides A, U, C and G.

6. The siRNA-related biomaterial according to any one of claims 1 to 5, characterized in that: Is any of the following: (1) a vector for expressing the siRNA; (2) a host cell carrying the siRNA or the vector; (3) a reagent containing the siRNA, or (1) the vector, or (2) the host cell; (4) A pharmaceutical composition containing the siRNA.

7. The biomaterial according to claim 6, characterized in that The pharmaceutical composition may also contain androgen or androgen receptor inhibitor.

8. The biomaterial according to claim 6 or 7, characterized in that: The pharmaceutical composition contains pharmaceutically acceptable carriers or excipients.

9. The biomaterial according to claim 8, characterized in that The pharmaceutically acceptable carrier includes liposomes, micelles, metal particles, or polymer particles.

10. Use of the siRNA according to any one of claims 1 to 5 or the biomaterial according to any one of claims 6 to 9 in the preparation of a drug for preventing or treating prostate cancer.

11. The use according to claim 10, characterized in that: The prostate cancer is advanced prostate cancer or castration-resistant prostate cancer.

12. A method for preventing or treating prostate cancer, characterized in that: The method comprises administering the siRNA according to any one of claims 1 to 5 or the biomaterial according to any one of claims 6 to 9 to a subject.

13. A method for inhibiting the expression of PRDX5 and / or GPX4 genes in cells, characterized in that: The method comprises contacting an effective amount of the siRNA according to any one of claims 1 to 5 or the biomaterial according to any one of claims 6 to 9 with cells, thereby inhibiting the expression of PRDX5 and / or GPX4 genes in the cells.

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