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微小 RNA-1202 通过 KCNQ1OT1-hsa-miR-1202-ETS1 调控通路在骨关节炎中发挥重要作用。

MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

机构信息

Department of Orthopaedics, No. 904th Hospital of the Joint Logistics Support Force of PLA, Liangxi District, Wuxi, 214044, Jiangsu, China.

出版信息

J Orthop Surg Res. 2020 Apr 6;15(1):130. doi: 10.1186/s13018-020-01655-0.

Abstract

BACKGROUND

This study aimed to explore the molecular mechanism of osteoarthritis (OA) and provide information about new genes as potential targets for OA treatment.

METHODS

Gene expression profile of GSE105027, including 12 OA serum samples (OA group) and 12 healthy serum samples (ctrl group), was downloaded. The differentially expressed miRNAs (DEMs) as well as miRNA-mRNAs interactions were investigated, followed by function and pathway investigation. Then the protein-protein interaction (PPI) network was performed. Furthermore, the long non-coding RNA (lncRNA)-miRNA-mRNA interactions (competing endogenous RNAs, ceRNAs) were investigated.

RESULTS

A total of 17 downregulated miRNAs were revealed between OA and ctrl groups. These DEMs such as has-miR-1202 were mainly enriched in GO functions like histone acetyltransferase binding and KEGG pathways like cellular senescence. The integrated PPI network analysis showed that has-miR-1202, has-miR-33b-3p, has-miR-940, has-miR-4284, and has-miR-4281 were 5 downregulated miRNAs in this network. Furthermore, the lncRNA-miRNA-mRNA interactions such as KCNQ1OT1-has-miR-1202-ETS1 were revealed in the present ceRNA network.

CONCLUSION

Key DEMs such as miR-33b-3p, miR-940, and miR-1202 may be involved in OA. miR-1202 may regulate OA development via histone acetyltransferase pathway binding function and cellular senescence pathway. Furthermore, KCNQ1OT1-has-miR-1202-ETS1 might be vital for the process of OA.

摘要

背景

本研究旨在探讨骨关节炎(OA)的分子机制,并为寻找 OA 治疗的新基因靶点提供信息。

方法

下载 GSE105027 基因表达谱,包括 12 例 OA 血清样本(OA 组)和 12 例健康血清样本(ctrl 组)。分析差异表达 miRNA(DEM)以及 miRNA-mRNA 相互作用,然后进行功能和通路分析。再进行蛋白质-蛋白质相互作用(PPI)网络分析。此外,还研究了长链非编码 RNA(lncRNA)-miRNA-mRNA 相互作用(竞争内源性 RNA,ceRNA)。

结果

OA 和 ctrl 组之间共发现 17 个下调的 miRNA。这些 DEMs,如 has-miR-1202,主要富集在 GO 功能如组蛋白乙酰转移酶结合和 KEGG 通路如细胞衰老。整合的 PPI 网络分析显示,has-miR-1202、has-miR-33b-3p、has-miR-940、has-miR-4284 和 has-miR-4281 是该网络中 5 个下调的 miRNA。此外,还揭示了 KCNQ1OT1-has-miR-1202-ETS1 等 lncRNA-miRNA-mRNA 相互作用在本 ceRNA 网络中。

结论

关键的 DEMs,如 miR-33b-3p、miR-940 和 miR-1202,可能参与 OA 的发生。miR-1202 可能通过组蛋白乙酰转移酶结合功能和细胞衰老途径调节 OA 的发生。此外,KCNQ1OT1-has-miR-1202-ETS1 可能对 OA 过程至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba90/7137223/781d5733ec28/13018_2020_1655_Fig1_HTML.jpg

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