N6-methyladenosine related regulatory factors in osteoarthritis: bioinformatics analysis and experimental validation

doi:10.12307/2024.224

Abstract

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.

Key words: osteoarthritis, N6-methyladenosine, bioinformatics, machine learning, regulator factor, chondrocyte, experimental verification

CLC Number:

Yuan Changshen, Liao Shuning, Li Zhe, Guan Yanbing, Wu Siping, Hu Qi, Mei Qijie, Duan Kan. N6-methyladenosine related regulatory factors in osteoarthritis: bioinformatics analysis and experimental validation[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(11): 1724-1729.

Figures/Tables 8

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