Biomarker for rheumatoid arthritis, diagnostic kit and application

Abstract

The invention relates to the technical field of biological detection, in particular to a rheumatoid arthritis biomarker, a diagnostic kit and application. The biomarker is miR-103a-3p, and the biomarker is miR-103a The application comprises the application in preparation of products for differential diagnosis of rheumatoid arthritis and osteoarthritis; the invention also relates to an application in preparation of a product for rheumatoid arthritis screening. The invention also relates to an application in preparation of products for rheumatoid arthritis disease prediction. Experimental results show that miR-103a-3p participates in the occurrence and development process of RA by targeting DKK1, and can be considered as a new detection or treatment target of rheumatoid arthritis, and a new application direction is provided for diagnosis and treatment of RA.

Description

Technical Field

[0001] The present invention relates to the field of biological detection technologies, and particularly to a biomarker for rheumatoid arthritis, a diagnostic kit, and applications thereof. Background Art

[0002] Rheumatoid arthritis (RA) is a systemic autoimmune disease with an unclear current pathogenesis. It is mainly clinically manifested by chronic, progressive, invasive, and disabling joint lesions. Along with the development of the disease, it can lead to damage to the bone and cartilage adjacent to the joints, ultimately resulting in joint deformity and even loss of joint function, seriously affecting the quality of life of patients and having a very high disability rate. Early diagnosis of rheumatoid arthritis is crucial for actively treating irreversible damage to joints or organs and controlling chronic inflammation through the widespread use of conventional drugs and anti-rheumatic arthritis drugs. However, some RA patients with negative rheumatoid factor and cyclic citrullinated peptide antibodies may be misdiagnosed, and the delay may lead to deterioration of the clinical prognosis. Therefore, exploring the etiology and pathogenesis of RA has important value for the early prevention, early diagnosis, and effective intervention of RA.

[0003] MicroRNA (miRNA) is an endogenous non-coding RNA that is 18 - 25 nt in length and is widely distributed in multiple eukaryotes. It regulates the expression of one or more genes by regulating the degradation or translational inhibition of mRNA. The molecular mechanisms of miRNA synthesis and function have been widely studied. With the development of molecular biology, the research on miRNA has become more extensive. miRNA is involved in a variety of physiological and pathological processes, and its expression level is closely related to the occurrence and development of diseases, especially cancer. The detection methods of miRNA have also become increasingly mature. However, its mechanism of action in RA has not been clarified.

[0004] In view of this, the present invention is specifically proposed. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a biomarker for rheumatoid arthritis, a diagnostic kit, and applications thereof.

[0006] The present invention proposes an application of a substance for detecting a biomarker, where the biomarker is miR-103a-3p, and the application includes one of the following applications:

[0007] a. Application in the preparation of a product for differential diagnosis between rheumatoid arthritis and osteoarthritis;

[0008] b. Application in the preparation of a product for screening rheumatoid arthritis;

[0009] c. Application in the preparation of a product for predicting the onset of rheumatoid arthritis.

[0010] Optionally, the substance for detecting the biomarker is a reagent for detecting the expression level of miR-103a-3p; preferably, it is a reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene; preferably, the reagent for detecting the expression level of miR-103a-3p or the reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes reagents for detecting the expression level by Northern blotting, fluorescence quantitative PCR, or microarray technology.

[0011] Optionally, the reagent for detecting the expression level of miR-103a-3p includes primers for detecting the expression level of miR-103a-3p; the sequences of the primers are preferably SEQ ID NO:1 to SEQ ID NO:2; the reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B; the sequences of the primers are preferably SEQ ID NO:1 to SEQ ID NO:4; the reagent for detecting the expression level of miR-103a-3p also includes reverse transcription reagents.

[0012] Optionally, diagnosis or screening is performed according to the detection results of the relative expression levels of miR-103a-3p and the housekeeping gene RNU6B in peripheral blood.

[0013] The present invention provides a kit for diagnosing rheumatoid arthritis. The kit includes a fluorescence quantitative detection reagent, and the fluorescence quantitative detection reagent contains primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B; preferably, the nucleotide sequences of the primers are as shown in SEQ ID NO:1 to SEQ ID NO:4.

[0014] Optionally, the fluorescence quantitative detection reagent also contains 2×SYBR qPCR mix; the concentration of the primers is 5 to 20 μM, preferably 10 μM.

[0015] Optionally, the kit also contains reverse transcription reagents. Preferably, the reverse transcription reagents contain 5×RT MasterMix, enzyme-free water, and Stem-loop primers; the nucleotide sequence of the Stem-loop primers is as shown in SEQ ID NO:5; the concentration of the Stem-loop primers is 5 to 20 μM, preferably 10 μM.

[0016] The present invention provides the application of miR-103a-3p as a molecular biomarker in the preparation of a diagnostic reagent or kit for rheumatoid arthritis.

[0017] The present invention provides the use of miR-103a-3p inhibitor in the preparation of a reagent for inhibiting the increased expression levels of DKK1 and / or TAK1, preferably the use of miR-103a-3p inhibitor in the preparation of a drug for treating rheumatoid arthritis.

[0018] The present invention provides the use of miR-103a-3p inhibitor in the screening of a drug for treating rheumatoid arthritis.

[0019] The technical solution provided by the embodiments of the present invention has the following advantages compared with the prior art:

[0020] The experimental results of the present invention show that miR-103a-3p is involved in the occurrence and development of RA by targeting DKK1, and can be considered as a new detection or treatment target for rheumatoid arthritis, providing a new application direction for the diagnosis and treatment of RA.

[0021] Moreover, based on the high stability of miRNA in human blood, the present invention proposes that the detection of the relative levels of miR-103a-3p and the housekeeping gene RNU6B has good specificity and sensitivity for the early diagnosis and disease prediction of RA, and has great potential for translation from research to clinical application.

[0022] The specimen of the present invention is the peripheral blood of the subject, and the sample specimen is easy to obtain, has strong clinical operability and is non-invasive to the subject. Description of the Drawings

[0023] Figure 1 It is a clustering diagram of some miRNAs with abnormal expression screened by miRNA microarray in Example 1;

[0024] Figure 2 It is the differential expression of miR-103-3p in synovial tissues of RA and OA patients in Example 2;

[0025] Figure 3 It is the experimental result that the expression level of miR-103-3p is significantly down-regulated in RAFLS in Example 2;

[0026] Figure 4 It is a comparison diagram of the expression level differences of miR-103-3p between rheumatoid arthritis model mice and normal mice in Example 3;

[0027] Figure 5 It is a comparison diagram of the expression level differences of miR-103-3p between RA patients and healthy volunteers in Example 4;

[0028] Figure 6The relative cell migration number comparison graph when miR-103-3p is overexpressed and inhibited in FLS in Example 5;

[0029] Figure 7 The relative cell proliferation activity comparison graph when miR-103-3p is overexpressed and inhibited in FLS in Example 5;

[0030] Figure 8 The relative cell invasion number comparison graph when miR-103-3p is overexpressed and inhibited in FLS in Example 5;

[0031] Figure 9 Exogenous up-regulation of miR-103a-3p can improve the clinical score results of rheumatoid arthritis model animals in Example 6. Detailed implementation manners

[0032] In order to more clearly understand the above objects, features and advantages of the present invention, the solutions of the present invention will be further described below. It should be noted that, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

[0033] Many specific details are set forth in the following description in order to fully understand the present invention, but the present invention can also be implemented in other ways different from those described herein; obviously, the embodiments in the specification are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0034] The abbreviations described in this application are as follows;

[0035] miRNA: microRNA (microRNA);

[0036] RA: Rheumatoid arthritis (Rheumatoid arthritis);

[0037] OA: Osteoarthritis (Osteoarthritis);

[0038] FLS: Fibroblast-like synoviocytes (Fibroblast-like synoviocytes);

[0039] DKK1: Dickkopf-Related Protein 1 (Dickkopf-Related Protein 1);

[0040] TAK1: Transforming Growth Factor-Beta-Activated Kinase 1 (Transforming Growth Factor-Beta-Activated Kinase 1);

[0041] CIA: Collagen-Induced Arthritis.

[0042] In the embodiments of the present invention, total RNA of synovial fibroblasts of osteoarthritis patients and rheumatoid arthritis patients was extracted, and differential screening was performed by miRNA microarray. It was found that miR-103a-3p in rheumatoid arthritis patients was significantly down-regulated. The expression difference of miR-103a-3p was detected in the synovial tissue and synovial fibroblasts of rheumatoid arthritis patients by RT-qPCR.

[0043] To further verify whether miR-103a-3p can be used as a diagnostic or prognostic factor for RA, the levels of miR-103a-3p in the sera of healthy subjects, RA patients, and RA patients treated with TNF-α neutralizing monoclonal antibody (neuAb, adalimumab injection) were detected by RT-qPCR. The results showed that the expression level of miR-103a-3p was relatively high in the healthy control group, but was significantly down-regulated by thousands of times in RA patients. After treatment with TNF-neutralizing monoclonal antibody neuAb, the expression of miR-103a-3p in the sera of RA patients in complete remission was significantly restored. More specifically, compared with the reference gene (conventional method of biomolecular technology) RNU6B, the gene expression of miR-103a-3p in normal human blood was hundreds of times that of RNU6B, while the gene expression of miR-103a-3p in the blood of RA patients was one-tenth of that of RNU6B. The inversion of the expression levels of the two genes can be used as one of the criteria for the diagnosis and prognosis of RA. Under the condition of low expression, miR-103a-3p promoted the proliferation, invasion, and migration of synovial fibroblasts. Subsequently, through bioinformatics analysis and dual-luciferase reporter system, it was found that DKK1 and TAK1 were the target genes downstream of miR-103a-3p, and low levels of miR-103a-3p mediated osteoclast differentiation through the regulation of the target gene DKK1. Up-regulating the expression of miR-103a-3p in a rheumatoid arthritis animal model could significantly alleviate the progression of rheumatoid disease and bone destruction in the ankle joint. These results all indicate that miR-103a-3p is involved in the occurrence and development of RA by targeting DKK1, and can be used as a new detection or treatment target for rheumatoid arthritis, providing a new application direction for the diagnosis and treatment of RA.

[0044] The microRNA markers discovered in the embodiments of the present invention have good specificity and sensitivity for the early diagnosis and disease prediction of diseases, and miRNAs have high stability in human blood. Circulating miRNAs are considered promising biomarkers for diagnosis and disease prognosis. In addition, the transformation of miRNA-based therapies from research to clinical application has great potential.

[0045] In the first aspect of the embodiments of the present invention, there is provided an application of a substance for detecting a biomarker. Through differential screening by miRNA microarray, it is found that compared with OAFLS cells, there are about 380 miRNAs with changes in RAFLS cells, among which miR-103a-3p is significantly down-regulated. Subsequently, through experiments, it is determined that miR-103a-3p is used as a biomarker. The application includes one of the following applications:

[0046] a. Application in the preparation of a product for differential diagnosis between rheumatoid arthritis and osteoarthritis;

[0047] b. Application in the preparation of a product for screening rheumatoid arthritis;

[0048] c. Application in the preparation of a product for predicting the onset of rheumatoid arthritis.

[0049] As an improvement of the embodiments of the present invention, the substance for detecting the biomarker is a reagent for detecting the expression level of miR-103a-3p, preferably a reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene. Among them, the reagent for detecting the expression level of miR-103a-3p, or the reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes reagents for detecting the expression level of miR-103a-3p by Northern blotting, fluorescence quantitative PCR, microarray technology, etc. And fluorescence quantitative PCR is preferred. The sequences of the primers for detecting the expression level of miR-103a-3p by fluorescence quantitative PCR are preferably SEQ ID NO:1 to SEQ ID NO:2.

[0050] The reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B, and the sequences of the primers are preferably SEQ ID NO:1 to SEQ ID NO:4. The diagnostic criterion is to detect the relative levels of miR-103a-3p and the housekeeping gene RNU6B. The housekeeping gene RNU6B is stably expressed in the human body. Taking RNU6B as a reference, the 2 -ΔΔCt method is used to calculate the relative expression amount of the gene. The expression level of miR-103a-3p in normal people is higher than that of RNU6B or there is no significant difference from RNU6B, while a significantly lower expression level of miR-103a-3p than RNU6B can be judged as RA. The data processing method for significant differences is: all data are expressed as the mean ± SD of at least three independent replicates. The comparison of two groups of normally distributed data uses a two-sided student unpaired t-test. The comparison among multiple groups uses one-way analysis of variance. When P < 0.05, it is defined as a significant difference.

[0051] Moreover, the reagent for detecting the expression level of miR-103a-3p further includes a reverse transcription reagent.

[0052] As an improvement of the embodiment of the present invention, diagnosis or screening is performed according to the detection results of the relative expression levels of miR-103a-3p and the housekeeping gene RNU6B in peripheral blood. Peripheral blood sample specimens are easy to obtain, have strong clinical operability and are non-invasive to the subject.

[0053] The second aspect of the embodiment of the present invention provides a kit for diagnosing rheumatoid arthritis. The kit includes a fluorescence quantitative detection reagent, and the fluorescence quantitative detection reagent contains primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B; preferably, the nucleotide sequences of the primers are as shown in SEQ ID NO:1 to SEQ ID NO:4.

[0054] As an improvement of the embodiment of the present invention, the fluorescence quantitative detection reagent further contains 2×SYBR qPCR mix; the concentration of the primers is 5-20 μM, preferably 10 μM.

[0055] As an improvement of the embodiment of the present invention, the kit further contains a reverse transcription reagent. Preferably, the reverse transcription reagent contains 5×RT Master Mix (reverse transcriptase), RNase-free water, and Stem-loop primers; the nucleotide sequence of the Stem-loop primers is as shown in SEQ ID NO:5, and the concentration is 5-20 μM, preferably 10 μM.

[0056] Specifically, the primer sequences are shown in Table 1, and the kit composition is shown in Table 2.

[0057] Table 1

[0058]

[0059] Table 2

[0060]

[0061] The third aspect of the embodiment of the present invention provides the application of miR-103a-3p as a molecular marker in the preparation of a diagnostic reagent or kit for rheumatoid arthritis.

[0062] The fourth aspect of the embodiment of the present invention provides the application of an miR-103a-3p inhibitor in the preparation of a reagent for inhibiting the increased expression of DKK1 and / or TAK1, preferably the application of an miR-103a-3p inhibitor in the preparation of a drug for treating rheumatoid arthritis.

[0063] The fifth aspect of the embodiments of the present invention provides the use of miR-103a-3p inhibitor in screening drugs for the treatment of rheumatoid arthritis.

[0064] Example 1

[0065] In order to verify that miR-103a-3p plays an important role in the pathological process of RA, the inventor recruited 6 RA and OA patients who visited the Department of Rheumatology and Immunology, Xijing Hospital, Air Force Medical University. This study on human samples was approved and supervised by the Ethics Committee of Air Force Medical University.

[0066] First, TRIzol (Thermo Fisher Scientific (China) Co., Ltd.) was used to extract the total RNA of FLS cells from OA and RA patients according to the instructions, and differential screening was performed by miRNA microarray. The RA and OA patients included in the study had not received any drug therapy or anti-inflammatory therapy. Through miRNA microarray detection (Shanghai Kangcheng Biotech Co., Ltd.), the miRCURY TM LNA Array (v.18.0) chip produced by Exiqon (Denmark) was selected.

[0067] The detection results showed that compared with OA FLS cells, there were about 380 miRNAs with changes in RA FLS cells, among which miR-103a-3p was significantly down-regulated.

[0068] Figure 1 It is a clustering diagram of some abnormally expressed miRNAs.

[0069] Example 2

[0070] In order to further verify the chip screening results of miRNAs with abnormal expression identified by RNA-seq in RA patients and OA patients, the inventor collected synovial tissues from 10 OA patients and RA patients again, and quantitatively verified miR-103a-3p by qRT-qPCR. The experimental method referred to the instruction manual of the kit. The experimental results are as Figure 2 shown.

[0071] Figure 2 The experimental results of show that miR-103a-3p is lowly expressed in the synovial tissues of RA patients.

[0072] The expression of miR-103a-3p was verified in RA FLS cells, and the experimental results are as Figure 3 shown.

[0073] Figure 3The measurement results showed that miR-103a-3p was also lowly expressed in RA FLS cells compared with OA FLS cells, and this result was consistent with the microarray screening results.

[0074] Example 3

[0075] To verify the possibility of miR-103a-3p as a biomarker for RA detection, a collagen-induced arthritis (CIA) mouse model was constructed to simulate the pathogenesis of rheumatoid arthritis. The required DBA / 1 (H-2q), SPF-grade mice and feed were purchased from Beijing Huafukang Bioscience Co., Ltd., and the study was approved and supervised by the Animal Ethics Committee of Air Force Medical University.

[0076] The construction method of the collagen-induced arthritis (CIA) mouse model was referred to Reference 1 and Reference 2.

[0077] Bovine type II collagen (2 mg / mL) and complete Freund's adjuvant containing Mycobacterium tuberculosis (4 mg / mL) were injected intradermally at about 1-2 cm apart at the base of the mouse tail. Mice in the control group were injected with an equal amount of complete Freund's adjuvant as a blank control. After 28 days of immunization, mice with successful modeling and control group mice were selected according to the joint index, and blood was collected for quantitative RT-qPCR to detect the expression of miR-103-3p. The detection results are as Figure 4 shown.

[0078] Figure 4 The experimental results showed that miR-103-3p was lowly expressed in CIA mice compared with control group mice.

[0079] References

[0080] Reference 1. Brand, D. D., Latham, K. A., & Rosloniec, E. F. (2007). Collagen-induced arthritis. Nature protocols, 2(5), 1269-1275.

[0081] Reference 2. Inglis, J. J., Criado, G., Medghalchi, M., Andrews, M., Sandison, A.,

[0082] Feldmann, M., & Williams, R. O. (2007). Collagen-induced arthritis in C57BL / 6 mice is associated with a robust and sustained T-cell response to type II collagen. Arthritis research & therapy, 9(5), R113.

[0083] Example 4

[0084] Furthermore, to verify the feasibility of miR-103-3p as a diagnostic molecular biomarker for RA, peripheral blood was collected from 42 RA patients, 44 healthy volunteers, and 10 RA patients treated with neuAb (adalimumab injection). RNA in plasma was extracted, reverse transcribed, and the expression level of miR-103-3p in RA was detected and verified by quantitative RT-qPCR. A receiver operating characteristic curve was established to confirm the diagnostic efficacy of miR-103-3p in peripheral blood serum between RA patients and healthy controls. The detection results are as Figure 5 shown.

[0085] Figure 5 The experimental results show that the relative expression levels of miR-103-3p and the housekeeping gene RNU6B in peripheral blood can distinguish RA patients from healthy volunteers and can be used as a diagnostic biomarker in the blood of RA patients.

[0086] Example 5

[0087] Furthermore, to verify the effect of miR-103-3p on the biological functions of FLS, synovial fibroblasts from patients were extracted and, according to the 2000 instructions, miRNA mimics (agomiR-103a (miR-103a-3p mimics), Guangzhou Ribobio Co., Ltd.) and inhibitors (scramble agomiR (miR-103a-3p inhibitor), Guangzhou Ribobio Co., Ltd.) were used to overexpress and inhibit miR-103-3p, respectively. The proliferation, invasion, and migration abilities of FLS were detected by measuring cell viability, Transwell invasion assay, and scratch assay. The experimental results of the FLS migration ability are as Figures 6 to 8 shown.

[0088] Figures 6 to 8The experimental results show that the overexpression of miR-103-3p inhibits the proliferation, invasion and migration abilities of FLS, and bioinformatics analysis and dual-luciferase experiments verify that TAK1 and DKK1 are the direct targets of miR-103-3p. Moreover, miR-103-3p can regulate osteoclast differentiation through DKK1.

[0089] Example 6

[0090] Furthermore, to verify the feasibility of miR-103-3p as a therapeutic molecular target for RA, chemically modified miR-103a-3p mimics (agomiR-103a-3p, Guangzhou Ribobio Co., Ltd.) were used to upregulate the expression of miR-103a-3p in the joints of CIA model mice by local ankle joint administration.

[0091] The experimental method was as follows: Starting from the onset of arthritis, 5 nmol / 10 μL of chemically modified miR-103a-3p mimics (agomiR-103a-3p), negative control (scramble agomiR, Guangzhou Ribobio Co., Ltd.) or normal saline were injected into the ankle joint cavity of mice every three days for a total of 28 days. The onset of arthritis was monitored every two days until the 49th day. The experimental results are as Figure 9 shown.

[0092] Figure 9 The experimental results show that upregulating miR-103a-3p can improve the swelling level and clinical score of the feet of model animals, and is helpful to a large extent in inhibiting the progression of the disease. It significantly improves the bone damage of small joints and ankle joints of the feet of CIA mice, and alleviates the articular cartilage damage of CIA model mice.

[0093] The above are only specific embodiments of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments described herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Use of a substance for detecting a biomarker, characterized in that, The biomarker is miR-103a-3p; The application includes one of the following applications: a. Application in the preparation of products for differential diagnosis of rheumatoid arthritis and osteoarthritis; b. Application in the preparation of products for screening of rheumatoid arthritis; c. Application in the preparation of products for predicting the onset of rheumatoid arthritis.

2. The application according to claim 1, wherein The substance for detecting the biomarker is a reagent for detecting the expression level of miR-103a-3p; preferably a reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene; Preferably, the reagent for detecting the expression level of miR-103a-3p, or the reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes reagents for detecting the expression level by Northern blotting, fluorescence quantitative PCR, or microarray technology.

3. The application according to claim 2, wherein The reagent for detecting the expression level of miR-103a-3p includes primers for detecting the expression level of miR-103a-3p; the sequences of the primers are preferably SEQ ID NO:1 to SEQ ID NO:2; The reagent for detecting the relative expression level of miR-103a-3p and a housekeeping gene includes primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B; the sequences of the primers are preferably SEQ ID NO:1 to SEQ ID NO:4; The reagent for detecting the expression level of miR-103a-3p further includes a reverse transcription reagent.

4. The application according to claim 3, characterized in that Diagnosis or screening is performed according to the detection results of the relative expression levels of miR-103a-3p and the housekeeping gene RNU6B in peripheral blood.

5. A kit for diagnosing rheumatoid arthritis, characterized in that, The kit includes a fluorescence quantitative detection reagent, and the fluorescence quantitative detection reagent contains primers for detecting the expression levels of miR-103a-3p and the housekeeping gene RNU6B; Preferably, the nucleotide sequences of the primers are as shown in SEQ ID NO:1 to SEQ ID NO:

4.

6. The diagnostic kit according to claim 5, wherein, The fluorescence quantitative detection reagent further contains 2×SYBR qPCR mix; the concentration of the primers is 5 to 20 μM, preferably 10 μM.

7. The diagnostic kit according to claim 5, wherein The kit further contains a reverse transcription reagent. Preferably, the reverse transcription reagent contains 5×RT Master Mix, enzyme-free water, and Stem-loop primers; the nucleotide sequence of the Stem-loop primers is as shown in SEQ ID NO:5, and the concentration is 5 to 20 μM, preferably 10 μM.

8. Application of miR-103a-3p as a molecular biomarker in the preparation of a diagnostic reagent or kit for rheumatoid arthritis.

9. Application of an miR-103a-3p inhibitor in the preparation of a reagent for inhibiting the increased expression of DKK1 and / or TAK1; preferably, the application of the miR-103a-3p inhibitor in the preparation of a drug for treating rheumatoid arthritis.

10. Application of an miR-103a-3p inhibitor in screening for drugs for treating rheumatoid arthritis.

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