Use of mir-3120 and analog thereof in prevention and treatment of tumor and tumor cachexia

Abstract

The present invention relates to use of miR-3120 in the prevention and treatment of a tumor and tumor cachexia. Specifically, disclosed is miR-3120 or an analog thereof, or an expression vector expressing the sequence of miR-3120 or an analog thereof, or a method capable of editing miR-3120 expression. The present invention can significantly inhibit the tumor and improve the status of tumor cachexia, thereby preventing and treating the tumor and tumor cachexia.

Description

Application of miR-3120 and its analogues in the prevention and treatment of tumors and tumor cachexia Technical Field

[0001] This invention belongs to the field of biomedical technology. Specifically, this invention relates to the application of miR-3120 in the prevention and treatment of tumor cachexia. Background Technology

[0002] Cancer cachexia (also known as tumor cachexia, cancer cachexia, etc.) is a complication that occurs in the late stages of various malignant tumors. Approximately 50%-80% of cancer patients experience cancer cachexia to varying degrees, and 20% of cancer deaths are due to cancer cachexia or cachexia-related complications. Cancer cachexia has the highest incidence in digestive system cancers such as gastric cancer, pancreatic cancer, and colorectal cancer. According to data released by the National Health Center of China, the incidence of cancer in China continues to rise. For example, in 2022, there were approximately 4.8247 million new cancer cases and approximately 2.5742 million new cancer deaths in China. With an aging population, the number of patients with cancer cachexia will continue to increase.

[0003] The main clinical symptoms of cancer cachexia include irreversible loss of appetite, anorexia, persistent muscle atrophy, weight loss, fatigue, anemia, and hypoproteinemia. The causes of cancer cachexia are complex. The Clinical Diagnosis and Treatment Guidelines for Cancer Cachexia (2020 Edition) published by the Cancer Nutrition Committee of the Chinese Anti-Cancer Association point out that there is a lack of effective treatments for cancer cachexia in clinical practice. Currently, no drugs have been approved for the treatment of cancer cachexia in the United States. Existing treatment regimens are not very effective. Randomized clinical trials have shown that currently used drugs for cancer cachexia, including appetite stimulants such as progestin analogs, serotonin (5-HT) receptor antagonists, and anti-inflammatory drugs such as cyclooxygenase-2 (COX-2) inhibitors, cannot successfully reverse the abnormal metabolic state of cancer cachexia and are accompanied by risks such as increased thromboembolism and adrenal suppression. In addition, anti-tumor treatments such as radiotherapy and chemotherapy can also trigger an important symptom of cachexia, namely, muscle wasting.

[0004] Anorexia and weight loss are prominent characteristics of patients with cancer cachexia, and the degree of weight loss reflects the stage of cancer cachexia. Studies have shown that energy metabolism disorders may cause cancer cachexia. Hormonal signals produced by the pancreas (insulin) and adipose tissue (leptin, adiponectin) are involved in the regulation of energy metabolism and body weight. The severity of weight loss symptoms in patients with cancer cachexia is associated with a significant shortening of survival, and patients with severe weight loss have limited clinical treatment options (such as chemotherapy), and the treatment outcomes are also worse.

[0005] Current reports suggest that the pathogenesis of cachexia is closely related to the combined effects of hypothalamic neuronal signaling and multiple mediators, including hormones (such as leptin), neuropeptides (such as NPY), inflammatory cytokines (such as IL-1 and 6 and TNF), and neurotransmitters (such as serotonin and DA).

[0006] Numerous recent studies have revealed that cells, especially tumor cells, actively secrete small RNAs (miRNAs) into the extracellular space through exocrine mechanisms, thereby globally altering the body's immunity and metabolism. These actively secreted miRNAs were officially named "nucleic acid factors" at the end of 2023. Like cytokines and chemical factors, they participate in in vivo reprogramming and systemic regulatory processes. Existing research indicates that miRNAs are involved in various stages of tumorigenesis, such as proliferation, migration, invasion, and tumor angiogenesis.

[0007] The nucleic acid factor miR-3120 has a sequence length of 21 nt. Currently, there are few reports on the association between miR-3120 and cancer, and these reports lack systematicity and specificity. Existing research suggests that overexpression of miR-3120 may help suppress tumor cells. For example, in ovarian cancer, upregulation of miR-3120 expression can help suppress the expression of inflammatory factors related to endoplasmic reticulum stress, thereby alleviating acute inflammatory responses. In gallbladder cancer, upregulation of miR-3120 and its combination miRNAs can target and inhibit the expression of E2F3 in cancer cells, thereby inhibiting the mesenchymal transition process of gallbladder cancer cells and reducing their migration and invasion capabilities. However, other studies have found that overexpression of miR-3120 accompanies the development of cancer. For example, Wan et al. found that the expression level of miR-3120 in the serum of colorectal cancer patients was abnormally high. Early monitoring of miR-3120 levels in patient serum can help in the early diagnosis of colorectal cancer. Li et al. found that miR-3120 can target the expression of Axin2 to promote the stemness and invasiveness of cancer cells. Furthermore, Xu et al. found that overexpression of miR-3120 can promote the proliferation and migration of non-small cell lung cancer. Meanwhile, there is little research on the association between miR-3120 and tumor cachexia. Existing literature suggests that miR-3120 is associated with tumor inflammation and anorexia: in ovarian cancer, upregulation of miR-3120 expression can help alleviate acute inflammatory responses; in pancreatic cancer, tumor-induced anorexia nervosa appears earlier than tumor cachexia, and miR-3120 targets the tumor-secreted signaling factor INSL3, which triggers anorexia nervosa in pancreatic cancer patients.

[0008] In summary, there is currently a lack of a method in this field for the effective prevention and treatment of tumors and tumor cachexia using nucleic acid factors.

[0009] Summary of the Invention

[0010] Through extensive literature review, the inventors discovered that the nucleic acid factor miR-3120, due to its correlation with some tumor inflammatory responses and anorexia, speculated that it might have the potential to treat tumor cachexia. After long-term research, they revealed for the first time that the nucleic acid factor miR-3120, at extremely low dose levels, can inhibit tumors, improve weight loss and reduced food intake caused by tumor cachexia, and improve the overall survival status of animals with tumor cachexia, thereby inhibiting tumors, slowing the progression of cachexia, and achieving therapeutic effects.

[0011] In a first aspect, the present invention provides the use of a pharmaceutical composition in the preparation of a medicament for the prevention and treatment of tumor cachexia; wherein the pharmaceutical composition comprises: miR-3120 or an analogue thereof, or an expression vector expressing the sequence of said miR-3120 or an analogue thereof, or an ingredient capable of editing miR-3120 expression as an active ingredient.

[0012] Wherein, the miR-3120 or its analogues are selected from any of the following sequences (1) or (2):

[0013] (1) The complete form of miR-3120, the -3p form of miR-3120, the -5p form of miR-3120, or the seed sequence of miR-3120 (3-8nt);

[0014] (2) The precursor form of the sequence described in (1) can generate the corresponding sequence described in (1) in vivo.

[0015] In this invention, the various miR-3120 or analogue sequences may be unmodified or optionally chemically modified.

[0016] In another preferred embodiment, the miR-3120 or its analogues are selected from the group consisting of: the complete form of miR-3120, or its -3p and -5p forms, or its seed sequence; or a precursor form of the above sequences, which can generate the complete form of miR-3120, its -3p and -5p forms, or its seed sequence in vivo.

[0017] In another preferred embodiment, the miR-3120 or its analogues are sequences selected from the group consisting of the -3p form of miR-3120 and the -5p form of miR-3120.

[0018] In another preferred embodiment, the complete sequence of miR-3120 is: 5'-GUCAUGUGACUGCCUGUCUGUGCCUGCUGUACAGGUGAGCGGAUGUUCUGCACAGCAAGUGUAGACAGGCAGACACAUGAC-3' (SEQ ID No. 1);

[0019] Its -3p sequence is: 5'-CACAGCAAGUGUAGACAGGCA-3' (SEQ ID No. 2);

[0020] Its -5p sequence is: 5'-CCUGUCUGUGCCUGCUGUACA-3' (SEQ ID No. 3). In another preferred embodiment, the expression vector is selected from the group consisting of plasmids, AAV, lentiviruses, or combinations thereof.

[0021] In another preferred embodiment, the expression vector comprises a plasmid.

[0022] In another preferred embodiment, the expression vector or plasmid contains a promoter, an origin of replication, and a marker gene.

[0023] In another preferred embodiment, the expression vector contains an expression cassette for expressing miRNA.

[0024] In another preferred embodiment, the expression cassette (i.e., polynucleotide) is double-stranded and has the following structure:

[0025] Promoter - attB1 - optional tag protein (e.g., GFP or emGFP, or none) - 5' miRNA flanking sequence - stem-loop structure containing target sequence - 3' miRNA flanking sequence - optional repeat expression sequence - attB2 - optional TKPA element;

[0026] In another preferred embodiment, the pharmaceutical composition is a liposome formulation.

[0027] In another preferred embodiment, the expression vector may upregulate / downregulate miR-3120, or the -3p form of miR-3120, or the -5p form of miR-3120.

[0028] In another preferred embodiment, the expression vector or precursor and the linker to the target gene are selected from the group consisting of polypeptides, proteins, or small molecules.

[0029] In another preferred embodiment, the method for editing miR-3120 expression is CRISPR.

[0030] In another preferred embodiment, the expression vector further contains a second active ingredient; preferably, the second active ingredient is selected from the group consisting of recombinant plasmids, peptide chains, CAR-T cells, or combinations thereof.

[0031] In another preferred embodiment, the second active ingredient comprises elements selected from the group consisting of: targeting elements, and / or antitumor / cachexia-enhancing elements.

[0032] In another preferred embodiment, the expression vector can generate the active ingredient miR-3120 sequence in vivo or promote / inhibit the expression of the gene.

[0033] In another preferred embodiment, the pharmaceutical composition is used at a stage selected from the group consisting of: pre-cachexia, cachexia, and refractory cachexia caused by cancer development.

[0034] In another preferred embodiment, the drug is a dosage form selected from the group consisting of tablets, capsules, injections, aerosols, ointments, powders for injection, powder inhalers, sprays, granules, or combinations thereof.

[0035] In another preferred embodiment, the route of administration of the drug includes: oral administration, intravenous injection, subcutaneous injection, intramuscular injection, local administration, sustained-release administration, inhalation administration, etc.

[0036] In another preferred embodiment, the dosage form of the pharmaceutical composition further includes sprays, aerosols, powders, volatile liquids, external solutions, lotions, pour-over solutions, liniments, poultices, plasters, rubber plasters, ointments, hard plasters, pastes, eye drops, nasal drops, ophthalmic ointments, mouthwashes, sublingual tablets, or suppositories.

[0037] In another preferred embodiment, the formulation is a liquid dosage form.

[0038] In another preferred embodiment, the dosage form is an injection, preferably an intravenous injection or an intraperitoneal injection.

[0039] In another preferred embodiment, when the miR-3120 small nucleic acid drug is used as the active pharmaceutical ingredient in the treatment of tumor cachexia, the dosage based on its core sequence is 0.3 μg to 60 μg / person / time, i.e., 0.005-1 μg / kg body weight, with body weight calculated as 60 kg.

[0040] In another preferred embodiment, miR-3120 is the active pharmaceutical ingredient, and its effective concentration in the human circulatory system, based on its core sequence, is 1×10⁻⁶. 4 ~1×10 9 The effective concentration in the target organ is 1 × 10⁻¹¹ copies / μl. 4 ~1×10 9 copies / mg.

[0041] In another preferred embodiment, miR-3120 is the active pharmaceutical ingredient, and its effective concentration in the human circulatory system, based on its core sequence, is 5 × 10⁻⁶. 4 copies / μl, 1×10 5 copies / μl, 5×10 5 copies / μl, 1×10 6 copies / μl, 5×10 6 copies / μl, 1×10 7 copies / μl, 5×10 7 copies / μl, 1×10 8 copies / μl, or 5×10 8 copies / μl.

[0042] In another preferred embodiment, the tumor is selected from the group consisting of: lung cancer, colon cancer, liver cancer, stomach cancer, and pancreatic cancer.

[0043] A second aspect of the present invention provides a method for inhibiting tumor cell migration in vitro, the method comprising: administering an effective amount of a pharmaceutical composition to the target to be inhibited, wherein the composition comprises: miR-3120 or an analogue thereof, or an expression vector expressing the sequence of said miR-3120 or an analogue thereof, or an ingredient capable of editing miR-3120 expression as an active ingredient;

[0044] The miR-3120 or its analogues are selected from the group consisting of: the complete form of miR-3120, its -3p and -5p forms, or its seed sequence (3-8 nt); or a nucleic acid sequence that is inversely complementary to the above sequences, or a nucleic acid sequence in a precursor form, wherein the precursor form can generate the nucleic acid sequence in vivo; wherein the sequence may optionally be chemically modified.

[0045] The complete sequence of miR-3120 is: 5'-GUCAUGUGACUGCCUGUCUGUGCCUGCUGUACAGGUGAGCGGAUGUUCUGCACAGCAAGUGUAGACAGGCAGACACAUGAC-3' (SEQ ID No. 1);

[0046] Its -3p sequence is: 5'-CACAGCAAGUGUAGACAGGCA-3' (SEQ ID No. 2);

[0047] Its -5p sequence is: 5'-CCUGUCUGUGCCUGCUGUACA-3' (SEQ ID No. 3).

[0048] In another preferred embodiment, the tumor cells are selected from the group consisting of: lung cancer cells, colon cancer cells, liver cancer cells, gastric cancer cells, and pancreatic cancer cells.

[0049] In another preferred embodiment, the lung cancer cells are selected from the group consisting of: A549[A-549] (human non-small cell lung cancer cells), HCC827 (human non-small cell lung cancer cells), NCI-H1299 (human non-small cell lung cancer cells), 95-D[PLA-801D] (human highly metastatic lung cancer cells), Calu-1 (human lung cancer cells), Calu-3 (human lung adenocarcinoma cells (pleural effusion)), LTEP-a-2 (human lung adenocarcinoma cells), MSTO-211H (human lung cancer cell line), and NCI-H1650 (human non-small cell lung cancer cells). NCI-H292 (human lung cancer cells (lymph node metastasis)), SK-MES-1 (human lung squamous cell carcinoma cells), T84 (human colon adenocarcinoma lung metastasis cells), A-427 (human lung cancer cells), NCI-H1395 (human lung adenocarcinoma cells), NCI-H1975 (human lung adenocarcinoma cells), NCI-H460[H460] (human large cell lung cancer cells), NCI-H661 (human large cell lung cancer cells), NCI-H157 (human non-small cell lung adenocarcinoma cells), NCI-H1688 (human classic small cell lung cancer cells) NCI-H1703 (human lung squamous cell carcinoma cells), NCI-H2087[H2087] (human non-small cell lung adenocarcinoma cells), NCI-H209[H209] (human small cell lung cancer cells), NCI-H2170 (human lung squamous cell carcinoma cells), NCI-H2227 (human small cell lung cancer cells), NCI-H226[H226] (human lung squamous cell carcinoma cells), NCI-H23 (human non-small cell lung cancer cells), NCI-H358 (human non-small cell lung cancer cells), NCI-H446[H446] (human small cell lung cancer cells) The following cells were identified: NCI-H520 (human lung squamous cell carcinoma cells), NCI-H524 (human non-small cell lung cancer cells), NCI-H596 (human lung adenosquamous cell carcinoma cells), NCI-H838 (human non-small cell lung cancer cells), QG-56 (human lung squamous cell carcinoma cells), NCI-H441 (human lung adenocarcinoma cells), A549 / DDP (human lung adenocarcinoma cisplatin-resistant strain), DMS153 (human small cell lung cancer cells), NCI-H2228 [H2228; H-2228] (human lung cancer cells), and NCI-H2347 (human lung cancer cells).

[0050] In another preferred embodiment, the colon cancer cells are selected from the group consisting of: SW480, SW620, SW1116, LOVO, HCT116, HCT-15, HT-29, LS180, LS174T, NCI-H716, Caco-2, COLO 205, COLO 320, COLO 320DM, CT26.WT, DLD-1, RKO, RKO-E6, RKO-AS45-1, T84, or combinations thereof.

[0051] In another preferred embodiment, the gastric cancer cells are selected from the group consisting of: MKN45, HGC-27, MGC803, SGC-7901, AGS, MKN74, MKN45, and SNU-1.

[0052] In another preferred embodiment, the liver cancer cells are selected from the group consisting of: HepG2, HepG2.2.15, Hep3B, Huh7, Hep3B, SNU-449, SNU-398, SNU182, MHCC97-H, MHCC97-L, MHCC-LM3, PLC / PRF / 5, Li-7, or combinations thereof.

[0053] In another preferred embodiment, the pancreatic cancer cells are selected from the group consisting of: PANC-1 (BC-C-HU-041), MIA PaCa-2 (BC-C-HU-053), Capan-2 (BC-C-HU-092), BxPC-3, Capan-1, AsPC-1, and CFPAC-1.

[0054] A third aspect of the present invention provides the use of a composition in the preparation of a medicament for the prevention and treatment of tumors; wherein the composition comprises: miR-3120 or an analogue thereof, or an expression vector expressing the sequence of said miR-3120 or an analogue thereof, or an ingredient capable of editing miR-3120 expression as an active ingredient;

[0055] The miR-3120 or its analogues are selected from the group consisting of: the complete form of miR-3120, its -3p and -5p forms, or its seed sequence (3-8 nt); or nucleic acid sequences complementary or reverse complementary to the above sequences, or nucleic acid sequences in their precursor form, wherein the precursor form can generate the nucleic acid sequence in vivo; wherein the sequence may optionally be chemically modified.

[0056] The complete sequence of miR-3120 is: 5'-GUCAUGUGACUGCCUGUCUGUGCCUGCUGUACAGGUGAGCGGAUGUUCUGCACAGCAAGUGUAGACAGGCAGACACAUGAC-3' (SEQ ID No. 1);

[0057] Its -3p sequence is: 5'-CACAGCAAGUGUAGACAGGCA-3' (SEQ ID No. 2);

[0058] Its -5p sequence is: 5'-CCUGUCUGUGCCUGCUGUACA-3' (SEQ ID No. 3).

[0059] In another preferred embodiment, the tumor is selected from the group consisting of: lung cancer, colon cancer, liver cancer, stomach cancer, and pancreatic cancer.

[0060] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0061] Figure 1 shows the experimental results of the effect of miR-3120 on the migration of H292 cells in Example 7;

[0062] Figure 2 shows the experimental results of the effect of miR-3120 on H460 cell migration in Example 8;

[0063] Figure 3 shows the experimental results of the effect of miR-3120 on the invasion of SW620 cell line in Example 9;

[0064] Figure 4 shows the experimental results of miR-3120 on tumor cachexia nude mice in Example 10 (a is food intake, b is water intake, c is weight loss rate).

[0065] Figures 5 and 6 are ultrasound images of the tumors in monkeys with malignant tumors and tumor cachexia before treatment in Example 11.

[0066] Figures 7, 8, 9 and 10 are ultrasound images taken after three weeks of treatment and three weeks of drug withdrawal in Example 11. Detailed Implementation

[0067] The inventors conducted extensive and in-depth research on tumors and tumor-induced cachexia and its related miRNAs, discovering a strong correlation between miR-3120 and the generation and development of tumor cachexia. Furthermore, administering miR-3120 to the target population at extremely low doses can increase food and water intake in cachexia, reverse weight loss, improve activity levels, and ultimately improve / treat cachexia. Based on this, the inventors developed this invention.

[0068] Tumor cachexia

[0069] As used in this article, the terms "cancer cachexia" and "cancer cachexia" are used interchangeably, both referring to a specific form of malnutrition in patients with advanced malignant tumors. Currently, the generally accepted manifestations of cachexia mainly include: persistent skeletal muscle wasting, with or without adipose tissue loss. Cancer cachexia is a common complication in patients with advanced malignant tumors. Currently, approximately 60%–80% of patients with advanced malignant tumors develop cachexia, and about 20% of cancer patients die from it. Cancer cachexia is unresponsive to conventional cancer treatments, and conventional nutritional therapy cannot completely alleviate it, ultimately leading to a multifactorial syndrome of progressive functional impairment. Therefore, effective interventions for cancer cachexia are of great significance for the long-term survival of patients with advanced malignant tumors.

[0070] microRNA

[0071] MicroRNAs (miRNAs) are a class of endogenous, short-chain RNAs, approximately 20-24 nucleotides in length. These non-coding RNAs participate in the post-transcriptional regulation of various target gene expression. Almost all cell types release miRNAs into the circulatory system passively (e.g., via apoptotic bodies) or actively (e.g., in exosomes or microvesicles). These molecules can influence the homeostasis of other tissues through paracrine signaling mechanisms or trigger pathogenic mechanisms, including the transformation of normal cells into tumor cells and the promotion of tumor cell proliferation.

[0072] Studies have shown that miRNAs target and participate in various cellular and molecular pathogenesis mechanisms through changes in their expression levels, playing a crucial role in tumor development and progression. The expression profile of miRNAs changes under different physiological states. Even the same miRNA can perform different functions at different stages of the same disease, and its expression level changes accordingly. For example, in ischemia-reperfusion, miR-214 expression is downregulated in the early hypoxic state to combat the hypoxic environment. After reperfusion, miR-214 expression is upregulated to promote tissue repair. Therefore, diseases can be comprehensively treated by upregulating / downregulating the same miRNA.

[0073] The inventors discovered that in animal models of tumor cachexia, the expression of multiple miRNAs, including miR-3120, is abnormal. Animals with abnormal miR-3120 expression are more likely to progress to cachexia. Furthermore, the expression levels of -3p and -5p of miR-3120 show abnormalities at different stages of disease progression. Therefore, in vivo delivery of small nucleic acid drugs (including selectively providing the full-length sequence, -3p form, or -5p form, or corresponding expression vectors of these forms, depending on disease progression) can regulate the expression of miR-3120 in animals with tumor cachexia and improve cachexia-related indicators and overall survival status.

[0074] Pharmaceutical Uses of Small Molecule Nucleic Acid miR-3120

[0075] This invention provides a use of the small molecule nucleic acid miR-3120, specifically, the application of miR-3120 in the prevention and treatment of tumors and tumor cachexia.

[0076] Since miR-3120 can effectively improve the cachexia state in tumor cachexia animals, when a therapeutically effective amount of miR-3120, or any of its precursor forms, expression vectors, or common pharmaceutical compositions that can be used for miRNA delivery, is administered to the treatment subjects, an improvement in the cachexia state can be effectively observed. In a preferred embodiment of the present invention, miR-3120 includes its full form, -3p form, and -5p form; the full form sequence of miR-3120 is: 5'-GUCAUGUGACUGCCUGUCUGUGCCUGCUGUACAGGUGAGCGGAUGUUCUGCACAGCAAGUGUAGACAGGCAGACACAUGAC-3' (SEQ ID No. 1);

[0077] Its -3p sequence is: 5'-CACAGCAAGUGUAGACAGGCA-3' (SEQ ID No. 2);

[0078] Its -5p sequence is: 5'-CCUGUCUGUGCCUGCUGUACA-3' (SEQ ID No. 3).

[0079] Preferably, the active ingredient of the drug is miR-3120 or a nucleic acid sequence that is completely identical or similar to it, and / or complementary or reverse complementary to it; and / or a nucleic acid sequence that is completely identical or similar to it, and / or complementary or reverse complementary to it, a seed sequence (3-8 nt); and / or the nucleic acid sequence after chemical modification; or a nucleic acid sequence in a precursor form thereof, the precursor form of which can generate the nucleic acid sequence in vivo.

[0080] In some cases, the administration properties of natural miRNAs can be improved and their bioavailability increased by chemical modification. In a preferred embodiment, the chemical modification includes nucleoside modification (including glycosidic and nucleobase modifications) and inter-nucleoside linkage modification. Nucleotide chemical modification does not include cases where the difference from naturally occurring RNA or DNA is only in the nucleobase sequence. In particular, since natural oligonucleotides have difficulty entering cells and are easily degraded by intracellular nucleases, resulting in poor efficacy, chemical modification of oligonucleotides can increase their bioavailability after administration.

[0081] In particular, without affecting the sequence function, a similar therapeutic effect can be achieved by giving the treatment subject a sequence that has a certain degree of homology with the desired sequence, such as a sequence that has 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, or 50% homology with the desired sequence (miR-3120 complete form, -3p form, -5p form).

[0082] The drug can also be administered via a suitable vector, such as plasmids, AAV, lentiviruses, or other vectors capable of gene editing. The drug can also be administered via other methods of upregulating / downregulating the expression of the desired miR-3120 sequence (intact miR-3120, -3p, or -5p form), such as CRISPR; or via a fusion expression structure; or by combining with a second active ingredient, which can be in any form, including recombinant plasmids, peptide chains, CAR-T cells, etc., and can be a targeting element or an anti-tumor / cachexia enhancement element.

[0083] The tumors described in vivo are various types of cancer, including lung cancer, colon cancer, liver cancer, pancreatic cancer, and stomach cancer; in vitro, they are typical cell lines of each cancer.

[0084] Preferably, the dosage forms of the small nucleic acid drug include: tablets, capsules, injections, aerosols, ointments, powders for injection, powder inhalers, sprays, granules, etc.

[0085] Preferably, the administration routes of the small nucleic acid drug include: oral administration, intravenous injection, subcutaneous injection, intramuscular injection, local administration, sustained-release administration, inhalation administration, etc.

[0086] Preferably, when the miR-3120 small nucleic acid drug is used as an active pharmaceutical ingredient in the treatment of tumors and tumor cachexia, the dosage according to its core sequence is: 0.3μg~60μg / person / time, that is, 0.005-1μg / kg body weight, with body weight calculated as 60kg.

[0087] Preferably, miR-3120 is the active pharmaceutical ingredient, and its effective concentration in the human circulatory system, based on its core sequence, is 1×10⁻⁶. 4 ~1×10 9 The effective concentration in the target organ is 1 × 10⁻¹¹ copies / μl. 4 ~1×10 9 copies / mg.

[0088] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0089] Example 1: Detection of miR-3120 content

[0090] Sample collection: At the experimental nodes, samples were collected for in vitro and in vivo efficacy tests. The collected cell samples, blood samples, tissue samples or organ samples were collected as required and stored in a -80℃ freezer for the detection of miR-3120 expression levels.

[0091] Total RNA extraction: Add an appropriate amount of RNA iso Plus to the sample (organ or tissue samples need to be pretreated by grinding, centrifugation, etc.), mix well and let stand at room temperature for 3-10 min; transfer the system to an enzyme-free centrifuge tube and pipette until no precipitate is formed; add an appropriate amount of chloroform to the system, mix well and let stand at room temperature for 3-10 min (the system will turn milky white); centrifuge at 12000 rpm for 10-20 min at 4℃; transfer the upper aqueous phase to a new enzyme-free centrifuge tube, add an appropriate amount of isopropanol, mix well and let stand at room temperature for 3-10 min; centrifuge the mixture at 12000 rpm for 5-20 min at 4℃, discard the supernatant and then add an appropriate amount of 75% ethanol, mix well and centrifuge at 4℃ for 5-15 min; discard the supernatant and dry the precipitate at room temperature; add an appropriate amount of DEPC water to the tube to dissolve the precipitate; take an appropriate amount of the solution for total RNA detection, and store the remainder at -80℃.

[0092] RNA reverse transcription: Prepare brand new RNase-free centrifuge tubes and label them; prepare the reverse transcription system according to the following ratio: DEPC water 3.5ul; AMV RT 5x Buffer 2ul; dNTP Mixture 1ul; AMV reverse transcriptase 0.5ul; reverse transcription primer (10uM) 2ul; template 2ul; transfer the system to a PCR instrument and reverse the transcription according to the following program: 16℃ for 30min, 37℃ for 60min, 85℃ for 10min, and 4℃ for ∞; the reverse transcription and qPCR primer information is shown in Table 1.

[0093] Table 1 Primer Information

[0094] qPCR quantitative detection: Prepare the qPCR reaction system according to the following ratio: DEPC water 5.9 μL; Sybr Green I 1 μL; upstream primer 1 μL; downstream primer 1 μL; PCR premix 10 μL; Rox reference dye 0.1 μL; template (reverse transcription product) 1 μL; and perform qPCR quantitative detection according to the procedure shown in Table 2.

[0095] Table 2 qPCR reaction procedure

[0096] Example 2: Culture of Tumor Cell Lines

[0097] Cell resuscitation: Quickly remove the desired cell line from the liquid nitrogen tank, place the cryovial in a 37-40℃ water bath and gently agitate until only a small amount of ice remains, then remove it; transfer the cell suspension from the cryovial to a 15ml centrifuge tube containing complete culture medium, centrifuge at 1200rpm for 10min, then transfer to a biosafety cabinet and aspirate the supernatant; resuspend the cells with an appropriate amount of complete culture medium, and then transfer them to a culture flask, observing uniform cell dispersion under a microscope; subsequently, transfer the culture flask to a CO2 incubator and culture at 37℃ with 5% CO2 until the cell confluence reaches 70-90%, then passage the cells.

[0098] Cell passage: Observe the cells in the culture flask under a microscope. When the confluence reaches 70-90%, transfer them to a biosafety cabinet. Aspirate the supernatant and wash 2-3 times with PBS. After aspirating the PBS, add trypsin to digest the cells. Observe the cells under a microscope when they shrink to a round shape, indicating that digestion is complete. Add an appropriate amount of culture medium and use a pipette to blow off the cells and collect the cell slurry into a centrifuge tube. Centrifuge the cell slurry at 1200 rpm for 10 min and aspirate the supernatant. Resuspend the cells in an appropriate amount of culture medium, aliquot the cells into culture flasks at a certain ratio, and transfer the culture flasks to a cell culture incubator at 37°C and 5% CO2 for culture. When the cell number and confluence reach the experimental requirements, proceed with subsequent experiments.

[0099] Cell plating: When the cell confluence in the culture flask reaches 70-90%, transfer the cells to a biosafety cabinet. Aspirate the culture medium and wash 2-3 times with PBS. After aspirating the PBS, add an appropriate amount of trypsin for digestion until the cells shrink to a round shape, then stop digestion. Add an appropriate amount of culture medium and gently pipette the cells to detach them. Collect the cell suspension in a centrifuge tube and centrifuge at 1200 rpm for 10 min. Aspirate the supernatant and resuspend the cells in an appropriate amount of culture medium. Transfer 20 μl of the cell suspension to a 1.5 ml EP tube, add trypan blue at a 1:1 ratio and mix well. Transfer 10 μl of the suspension to a hemocytometer and count the cells. Based on the counting results, transfer a certain amount of cell suspension to a 6-well plate and incubate the 6-well plate overnight at 37°C with 5% CO2.

[0100] Cell transfection: Prepare two 15ml centrifuge tubes, A and B. Add 2.5ml of basal culture medium and 75μl of lipo3000 to tube A, invert and mix well, then let stand for 5 min. Add 100μl of p3000 and 50μg of plasmid (blank solution for the control group; miR-3120 plasmid solution for the experimental group) to tube B, invert and mix well. The miR-3120 plasmid was synthesized by a manufacturer (Sangon Biotech) after providing the target sequence. After preparation, mix reagents A and B and let stand for 15 min. Add 250μl of the above mixture to each well of a 6-well plate, take site-specific photographs, and then transfer to a cell culture incubator for culture at 37℃ and 5% CO2.

[0101] Cell collection: 48 h after transfection, cell growth was observed in each treatment group. The supernatant was aspirated from the 6-well plates, and the cells were washed with PBS. Then, trypsin was added to each well at a rate of 0.5 ml / well for digestion. After digestion, an appropriate amount of complete culture medium was added, and the cells were thoroughly mixed by pipetting. The cell suspension from each group was collected, centrifuged at 1200 rpm for 10 min, the supernatant was aspirated, and the cells were resuspended in PBS and aliquoted. The cell suspension was stored at -80°C for subsequent experiments. (For samples used in qPCR quantification, RNAiso Plus was added at a rate of 1 ml / well for lysis for 10 min, and the samples were transferred to EP tubes and stored at -80°C.)

[0102] Example 3: Detection of miR-3120 expression in H292 cells

[0103] H292 cells were cultured and transfected according to the cell culture method in Example 2. The RNA expression level after transfection was collected, RNA was extracted and detected by the method described in Example 1.

[0104] Table 3. Expression effect of miR-3120 transfection in H292 cells

[0105] Note: LOQ indicates below the minimum detection limit.

[0106] The results are shown in Table 3. Compared with the control group, the expression level of miR-3120 was higher, reaching 1.08E+06 copies / μl, indicating that the miR-3120 plasmid was effectively transfected into H292 cells and that the miR-3120 plasmid could effectively express miR-3120 in the cells.

[0107] Example 4: Effect of miR-3120 on the proliferation of H292 cell line

[0108] H292 cells were cultured according to the cell culture method described in Example 2. During the cell plating stage, H292 cells were cultured at a density of 2*102. 4 The plasmid was seeded into 96-well plates at a concentration of 100 ng / well for culture. For transfection, the transfection reagent (with proportions consistent with Example 2) was prepared and added at a concentration of 100 ng / well. The 96-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2.

[0109] CCK8 assays were performed on each treatment group at 0h, 24h, 48h, and 72h. 10 μl of CCK8 reagent was added to each selected culture well, and the wells were then transferred to a cell culture incubator at 37℃ and 5% CO2 for incubation. After 2 hours of incubation, the OD450 value of the corresponding wells was measured using a microplate reader.

[0110] Compared with the control group, the inhibition rate of miR-3120 transfection reached 58.97% after 72 hours of culture. This shows that miR-3120 has a significant inhibitory effect on the proliferation of H292 cells.

[0111] Example 5: Effect of miR-3120 on the proliferation of SW620 cell line

[0112] SW620 cells were cultured according to the cell culture method described in Example 2. During the cell plating stage, SW620 cells were cultured at a density of 5*102. 3 The plasmid was seeded into 96-well plates at a concentration of 100 ng / well for culture. For transfection, the transfection reagent (with proportions consistent with Example 2) was prepared and added at a concentration of 100 ng / well. The 96-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2.

[0113] CCK8 assays were performed on each treatment group at 0h, 24h, 48h, and 72h. 10 μl of CCK8 reagent was added to each selected culture well, and the cells were then transferred to a cell culture incubator at 37℃ and 5% CO2 for incubation. After 2 hours of incubation, the OD450 value of the corresponding wells was measured using a microplate reader. Compared with the control group, the inhibition rate of miR-3120 transfection reached 55.09% after 72 hours of culture. This indicates that miR-3120 significantly inhibits the proliferation of SW620 cells.

[0114] Example 6: Effect of miR-3120 on the proliferation of HepG2 cell line

[0115] HepG2 cells were cultured according to the cell culture method described in Example 2. During the cell plating stage, HepG2 cells were cultured at a density of 2*102. 4 The plasmid was seeded into 96-well plates at a concentration of 100 ng / well for culture. For transfection, the transfection reagent (with proportions consistent with Example 2) was prepared and added at a concentration of 100 ng / well. The 96-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2.

[0116] CCK8 assays were performed on each treatment group at 0h, 24h, 48h, and 72h. 10 μl of CCK8 reagent was added to each selected culture well, and the wells were then transferred to a cell culture incubator at 37℃ and 5% CO2 for incubation. After 2 hours of incubation, the OD450 value of the corresponding wells was measured using a microplate reader.

[0117] Compared with the control group, the inhibition rate of miR-3120 transfection reached 80.14% after 72 hours of culture. It can be seen that miR-3120 showed a significant inhibitory effect on the proliferation of HepG2 cells.

[0118] Example 7: Effect of miR-3120 on cell migration of the H292 cell line

[0119] H292 cells were cultured according to the cell culture method described in Example 2. During the cell plating stage, H292 cells were cultured at a density of 1.5*102 6 The cells were seeded into 6-well plates at a concentration of 95-100%. When the cell confluence reached 95-100%, the plates were transferred to a biosafety cabinet. Using sterilized pipette tips or forceps, the cells were vertically scratched in the wells. After washing with PBS, 2 ml of basal culture medium was added to each well. For cell transfection, transfection reagents (with proportions consistent with Example 2) were prepared and added at a rate of 2500 ng / well. The 6-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2. The 6-well plates were photographed at 0 h, 24 h, 48 h, and 72 h (ensuring consistent photographic positions at all observation points).

[0120] As shown in Figure 1, in the control group, the scratches on the H292 cells in the wells had clearly healed after 24 hours of culture. After 48 hours of culture, the scratches had significantly reduced in size, and finally, after 72 hours of culture, no scratches were observed in the control group. In the experimental group, although the scratches in the wells showed some healing as culture progressed, the rate was significantly slower than in the control group. The scratches were still clearly visible at 72 hours of culture. The healing rate data also corroborated the observed experimental phenomenon: the healing rate of H292 cells in the experimental group was only 39.79% at 72 hours, while the healing rate of H292 cells in the control group had reached 100% at this time.

[0121] Example 8: Effect of miR-3120 on cell migration of H460 cell line

[0122] H460 cells were cultured according to the cell culture method described in Example 2. During the cell plating stage, H460 cells were cultured at a rate of 1×10⁶ cells / year. 6 The cells were seeded into 6-well plates at a concentration of 95-100%. When the cell confluence reached 95-100%, the plates were transferred to a biosafety cabinet. Using sterilized pipette tips or forceps, the cells were vertically scratched in the wells. After washing with PBS, 2 ml of basal culture medium was added to each well. For cell transfection, transfection reagents (with proportions consistent with Example 2) were prepared and added at a rate of 2500 ng / well. The 6-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2. The 6-well plates were photographed at 0 h, 24 h, 48 h, and 72 h (ensuring consistent photographic positions at all observation points).

[0123] As shown in Figure 2, in the control group, the scratches on H460 cells remained in a continuous healing state throughout the experiment, with an overall healing rate of 44.23% by the end of the experiment. While the experimental group cells also maintained a healing state during the experiment, the overall healing rate was only 21.46% by the end of the experiment. This demonstrates that miR-3120 inhibits the migration performance of the H460 cell line.

[0124] Example 9: Effect of miR-3120 on cell invasion of SW620 cell line

[0125] SW620 cells were cultured according to the cell culture method described in Example 2. Cell plating was performed within a Transwell chamber. First, the culture medium was diluted with matrix gel at a ratio of 6:1. After mixing, 60 μl of the diluted matrix gel was added to each well of the Transwell chamber. The culture plate was then placed in a 37°C, 5% CO2 incubator for 1 hour to allow the matrix gel to polymerize. After polymerization, the liquid in the upper chamber was aspirated in a biosafety cabinet, and 100 μl of basal culture medium was added to each well. The cells were then placed back in the incubator for hydration for 30 minutes. After the procedure, the cells were cultured using a 1*10... 5 SW620 cells were seeded into the chambers at a rate of 100 ng / well. For cell transfection, transfection reagents (with proportions consistent with Example 2) were prepared and added at a rate of 100 ng / well of plasmid. The 24-well plates were then transferred to a cell culture incubator and cultured at 37°C with 5% CO2.

[0126] After culture, the culture plate was transferred to a biosafety cabinet. The Transwell nests were carefully removed, the culture medium was aspirated, and the matrix gel and cells in the upper chamber were wiped away. The nests were then transferred to a new 24-well plate, and 4% paraformaldehyde was added for fixation for 15 min. After fixation, the fixative was aspirated, and crystal violet was added to the nests for staining for 10 min. After staining, any unbound crystal violet dye was removed. Before microscopic observation, the nests were carefully cleaned and then transferred to a microscope for observation. Five fields of view were randomly selected at an appropriate magnification for photographing, and the number of stained cells in each field of view was counted and statistically analyzed.

[0127] As shown in Figure 3, compared with the control group, the number of invasive cells in the miR-3120 treatment group was significantly reduced, and the invasive ability of the cells was significantly inhibited.

[0128] Example 10: The therapeutic effect of miR-3120 on nude mice with tumor cachexia

[0129] Model establishment: Twenty-four 6-week-old BALB / c nude mice (half male and half female) were purchased and, after quarantine and acclimatization, were used to establish a "nude mouse subcutaneous tumor-cache model". Cells cultured in Example 2 were used at a concentration of 1×10⁻⁶. 7 Nude mice were subcutaneously inoculated with cells at a dose of 200 μl per mouse. After inoculation, the nude mice were separated into cages according to sex and cultured. During the modeling period, the weight, clinical observation, tumor volume, water intake, and food intake of the nude mice in each cage were measured regularly. The tumor cachexia model was considered to be established when the food intake of the nude mice decreased and was accompanied by a weight loss of more than 10% or when tumor metastasis occurred.

[0130] In vivo efficacy study: After successful model establishment, nude mice were randomly divided into two groups, half male and half female. A blank control reagent (buffer solution) and miR-3120 injection were injected into each group via tail vein. The experimental group received 0.4 mg / kg (the core sequence dosage was approximately 8 μg / kg); the dosing frequency was once every 2 days, and the dosing period was 20 days. During the dosing process, the clinical status, tumor-free weight, and dietary indicators of the nude mice in each treatment group were observed.

[0131] As shown in Figure 4a, by the end of the experiment, the food intake of the experimental group nude mice was 30.19 g / d, while that of the control group nude mice was 28.99 g / d, representing a 4.14% increase in food intake compared to the control group. The weight loss of the experimental group nude mice was significantly slower than that of the control group, and their lifespan was also prolonged. As shown in Figure 4b, compared to the control group, the water intake of the mice in the experimental group remained stable and was higher than that of the control group. As shown in Figure 4c, the weight loss of the experimental group nude mice was approximately 8.77%, while the average weight loss rate of the control group nude mice was approximately 17.66%.

[0132] Furthermore, cage-side observations during the experiment showed that mice in the experimental group did not exhibit diarrhea, poor condition, lethargy, arched back, coldness, or death throughout the entire treatment period, a significant contrast to the control group. This demonstrates that miR-3120 significantly increased food and water intake in the nude mice in the lung cancer cachexia experimental group, salvaging weight loss during tumor cachexia and improving the overall condition of tumor cachexia.

[0133] Example 11: The therapeutic effect of miR-3120 on malignant tumors with tumor cachexia in monkeys

[0134] A 15-year-old female disabled deer macaque at the rescue station, weighing 4 kg, began experiencing abdominal distension, difficulty eating, and rapid weight loss in early 2023. Veterinary palpation revealed a hard mass. An abdominal ultrasound on April 29, 2023 (Figures 5-6) showed increased ascites, with the tumor measuring an average of 7.3 × 11.9 cm and a maximum cross-sectional measurement of 13.3 cm. Based on the examination results, the tumor was determined to be malignant, accompanied by tumor cachexia.

[0135] Dosing began in May 2023 at a dose of 0.5 mg / kg (approximately 3.5 μg / kg for the core sequence), administered once daily for 5 days followed by a 2-day break. After one month of continuous dosing, the tumor growth was halted, and the patient's diet and activity levels returned to normal.

[0136] An ultrasound examination was performed 20 days after drug withdrawal, and the results are shown in Figure 7-10. The average tumor size was 6.5 × 8.3 cm, with a maximum value of 8.9 cm on some sections. The ultrasound results showed that the tumor volume had significantly shrunk, and the deer monkeys were in good condition in terms of diet and activity.

[0137] Example 12: Study on the efficacy of miR-3120 in treating tumor cachexia

[0138] Model establishment: Thirty-six 6-week-old BALB / c nude mice (half male and half female) were purchased and, after quarantine and acclimatization, were used to establish a "nude mouse subcutaneous tumor-cache model". Cells cultured in Example 2 were used at a concentration of 1×10⁻⁶. 7 The nude mice were inoculated at a rate of 200 μl per mouse to establish the model. After inoculation, the mice were separated into cages according to sex and cultured. During the modeling period, the weight, clinical observation, tumor volume, water intake, and food intake of each cage of mice were measured regularly. The tumor cachexia model was considered to be established when the food intake of the nude mice decreased and was accompanied by a weight loss of more than 10% or when tumor metastasis occurred.

[0139] In vivo efficacy study: After successful model establishment, nude mice were randomly divided into three groups, half male and half female. Each group was injected via tail vein with a blank control reagent (blank control group), miR-3120 injection (experimental group), or cisplatin (positive control group). The dosage for the experimental group was 0.4 mg / kg (approximately 8 μg / kg for the core sequence); the dosing frequency was once daily for 14 days. During the dosing period, the clinical status, tumor-removed weight, and dietary indicators of each group of nude mice were observed.

[0140] The results showed that, compared with the blank control group, the tumor volume of the experimental group was significantly reduced, the tumor cachexia status was significantly improved, and the therapeutic effect was better than that of the positive control group.

[0141] In summary, this invention, through in vitro and in vivo pharmacodynamic experiments, confirms that miR-3120 has the effects of inhibiting the proliferation, migration, and invasion of tumor cells. In vivo, even with extremely low drug dosage, it can increase food and water intake in cachexia, reverse the weight loss process, improve activity level, and ultimately improve / treat cachexia.

[0142] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. Use of a pharmaceutical composition for the preparation of a medicament for the prevention and treatment of tumor anaplasia; wherein, The pharmaceutical composition comprises miR-3120 or an analogue thereof, or an expression vector expressing the sequence of miR-3120 or the analogue thereof, or a component capable of editing the expression of miR-3120 as an active ingredient. The miR-3120 or the analogue thereof is selected from any one of the following (1) or (2): (1) a complete form of miR-3120, a -3p form of miR-3120, a -5p form of miR-3120, or a seed sequence of miR-3120; (2) a precursor form sequence of the sequence as described in (1), which can generate the corresponding sequence as described in (1) in vivo.

2. Use according to claim 1, wherein The pharmaceutical composition comprises a sequence selected from any one of the following (1) or (2): (1) a complete form of miR-3120, a -3p form of miR-3120, a -5p form of miR-3120, or a seed sequence of miR-3120; (2) a precursor form sequence of the sequence as described in (1), which can generate the corresponding sequence as described in (1) in vivo.

3. The use according to claim 1, wherein The pharmaceutical composition comprises a sequence selected from the group consisting of a complete form of miR-3120, a -3p form of miR-3120, and a -5p form of miR-3120.

4. The use according to claim 1, wherein The expression vector is selected from the group consisting of a plasmid, an AAV, a lentivirus, or a combination thereof.

5. The use according to claim 1, wherein The expression vector can upregulate / downregulate the expression of a sequence selected from the group consisting of miR-3120, a -3p form of miR-3120, and a -5p form of miR-3120.

6. The use according to claim 1, wherein The linker of the expression vector or the precursor to the target gene is selected from the group consisting of a polypeptide, a protein, or a small molecule.

7. The use according to claim 1, wherein The method for editing the expression of miR-3120 is CRISPR.

8. The use according to claim 1, wherein The application amount of miR-3120 or its analog sequence as the active ingredient of the pharmaceutical composition in the application of preventing and treating tumor anaplasia is 0.005-1 μg / kg body weight, the effective concentration in the circulatory system is 1×10 4 ~1×10 9 copies / μl, and the effective concentration in the target organ is 1×10 4 ~1×10 9 copies / mg.

9. The use according to claim 1, wherein The tumor anaplasia comprises a pre-anaplasia stage, an anaplasia stage, and an anaplastic refractory stage caused by cancer development.

10. The use according to claim 1, wherein The drug is in a dosage form selected from the group consisting of a tablet, a capsule, an injection, an aerosol, a paste, a powder for injection, a powder for inhalation, a spray, a granule, a sustained-release preparation, or a combination thereof.

11. The use according to claim 1, wherein The tumor is selected from the group consisting of lung cancer, colon cancer, liver cancer, gastric cancer, and pancreatic cancer.

12. A method of inhibiting tumor cell migration in vitro, comprising contacting the tumor cells with a compound of claim 1. 5 The method comprises administering an inhibitory effective amount of a pharmaceutical composition to a subject in need of inhibition, and the composition comprises miR-3120 or an analogue thereof, or an expression vector expressing the sequence of miR-3120 or the analogue thereof, or a component capable of editing the expression of miR-3120 as an active ingredient. The miR-3120 or the analogue thereof is selected from any one of the following (1) or (2): (1) a complete form of miR-3120, a -3p form of miR-3120, a -5p form of miR-3120, or a seed sequence (3-8 nt) of miR-3120; (2) a precursor form sequence of the sequence as described in (1), which can generate the corresponding sequence as described in (1) in vivo. Preferably, the tumor cell is selected from the group consisting of a lung cancer cell, a colon cancer cell, a liver cancer cell, a gastric cancer cell, and a pancreatic cancer cell.

13. Use of a composition for the manufacture of a medicament for the prevention and treatment of tumors; wherein, The composition comprises: miR-3120 or an analogue thereof, or an expression vector expressing the sequence of the miR-3120 or the analogue thereof, or a component capable of editing the expression of the miR-3120 as an active ingredient; The miR-3120 or the analogue thereof is selected from any one of the following (1) or (2): (1) a complete form of miR-3120, a -3p form of miR-3120, a -5p form of miR-3120, or a seed sequence (3-8 nt) of miR-3120; (2) a precursor form sequence of the sequence as described in (1), which can generate the corresponding sequence as described in (1) in vivo; Preferably, the tumor is selected from the group consisting of lung cancer, colon cancer, liver cancer, gastric cancer, and pancreatic cancer.

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