Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China.
Department of Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai 519000, Guangdong, China.
Aging (Albany NY). 2020 Apr 13;12(7):5948-5976. doi: 10.18632/aging.102989.
The current study was aimed at exploring the potential roles and possible mechanisms of miR-10a-5p in osteoarthritis (OA). We performed RT-qPCR, Western blot, CCK8, EdU Assay, and flow cytometry assay to clarify the roles of miR-10a-5p in OA. Furthermore, the whole transcriptome sequencing together with integrated bioinformatics analyses were conducted to elucidate the underlying mechanisms of miR-10a-5p involving in OA. Our results demonstrated that miR-10a-5p was upregulated in OA and acted as a significant contributing factor for OA. A large number of circRNAs, lncRNAs, miRNAs, and mRNAs were identified by overexpressing miR-10a-5p. Functional enrichment analyses indicated that these differentially-expressed genes were enriched in some important terms including PPAR signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. A total of 42 hub genes were identified in the protein-protein interaction network including SERPINA1, TTR, APOA1, and A2M. Also, we constructed the network regulatory interactions across coding and noncoding RNAs triggered by miR-10a-5p, which revealed the powerful regulating effects of miR-10a-5p. Moreover, we found that HOXA3 acted as the targeted genes of miR-10a-5p and miR-10a-5p contributed to the progression of OA by suppressing HOXA3 expression. Our findings shed insight on regulatory mechanisms of miR-10a-5p, which might provide novel therapeutic targets for OA.
本研究旨在探索 miR-10a-5p 在骨关节炎(OA)中的潜在作用和可能机制。我们通过 RT-qPCR、Western blot、CCK8、EdU 检测和流式细胞术检测来阐明 miR-10a-5p 在 OA 中的作用。此外,还进行了全转录组测序和综合生物信息学分析,以阐明 miR-10a-5p 参与 OA 的潜在机制。研究结果表明,miR-10a-5p 在 OA 中上调,并作为 OA 的重要致病因素。通过过表达 miR-10a-5p 鉴定出大量 circRNAs、lncRNAs、miRNAs 和 mRNAs。功能富集分析表明,这些差异表达基因富集于一些重要术语,包括 PPAR 信号通路、PI3K-Akt 信号通路和 p53 信号通路。在蛋白质-蛋白质相互作用网络中总共鉴定出 42 个枢纽基因,包括 SERPINA1、TTR、APOA1 和 A2M。此外,我们构建了由 miR-10a-5p 触发的编码和非编码 RNA 之间的网络调控相互作用,揭示了 miR-10a-5p 的强大调控作用。另外,我们发现 HOXA3 是 miR-10a-5p 的靶向基因,miR-10a-5p 通过抑制 HOXA3 表达促进 OA 的进展。我们的研究结果揭示了 miR-10a-5p 的调控机制,为 OA 提供了新的治疗靶点。