N6-methyladenosine related regulatory factors in osteoarthritis:bioinformatics analysis and experimental validation
- VernacularTitle:N6-甲基腺苷相关调节因子与骨关节炎:生物信息学和实验验证分析
- Author:
Changshen YUAN
1
;
Shuning LIAO
;
Zhe LI
;
Yanbing GUAN
;
Siping WU
;
Qi HU
;
Qijie MEI
;
Kan DUAN
Author Information
- Keywords: osteoarthritis; N6-methyladenosine; bioinformatics; machine learning; regulator factor; chondrocyte; experimental verification
- From: Chinese Journal of Tissue Engineering Research 2024;28(11):1724-1729
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Increasing evidence suggests that N6-methyladenosine(m6A)regulators are closely associated with osteoarthritis and are considered to be a new direction in the prevention and treatment of osteoarthritis,but their specific mechanism of action is unknown. OBJECTIVE:To conduct a bioinformatics analysis of the osteoarthritis gene microarray dataset in order to explore the role of m6A in osteoarthritis and analyze the pathogenesis of osteoarthritis. METHODS:The m6A regulators associated with osteoarthritis and their expression were first extracted from the GSE1919 dataset in the GEO database using R software,and then the results were analyzed by gene difference analysis and GO and KEGG enrichment analyses.Subsequently,the results of protein-protein interaction network topology analysis and machine learning results were intersected to obtain the m6A Hub regulators,which were validated by in vitro cellular experiments. RESULTS AND CONCLUSION:A total of 16 osteoarthritis-related m6A regulators were extracted and 11 m6A differential regulators,including ZC3H13,YTHDC1,YTHDF3 and HNRNPC,were obtained by differential analysis.GO enrichment analysis showed that osteoarthritis-related m6A differential regulators played a role in the biological processes such as mRNA transport,RNA catabolism,and regulation of insulin-like growth factor receptor signaling pathway.(3)KEGG enrichment analysis showed that the differential regulators were mainly involved in the p53,interleukin-17 and AMPK signaling pathways.The combined protein-protein interaction network topology analysis and machine learning results obtained the m6A Hub regulator-YTHDC1.(5)The results of in vitro cellular experiments showed that there was a significant difference in the expression of m6A key regulator between the control and experimental groups(P<0.05).To conclude,YTHDC1 is closely related to the development of osteoarthritis,which is expected to be a molecular target of m6A for the treatment of osteoarthritis.
