Research Paper Volume 12, Issue 7 pp 5948—5976

Overexpression of miR-10a-5p facilitates the progression of osteoarthritis

Hui-Zi Li 1, 2, 3, *, , Xiang-He Xu 1, 2, 3, *, , Nan Lin 1, 2, 3, *, , Da-Wei Wang 1, , Yi-Ming Lin 1, , Zhong-Zhen Su 2, 3, 4, , Hua-Ding Lu 1, 2, 3, ,

  • 1 Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
  • 2 Department of Interventional Medicine, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai 519000, Guangdong, China
  • 3 Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong, China
  • 4 Department of Medical Ultrasonics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China
* Equal contribution

received: October 5, 2019 ; accepted: March 2, 2020 ; published: April 13, 2020 ;

https://doi.org/10.18632/aging.102989
How to Cite

Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

OA: Osteoarthritis; ncRNAs: Non-coding RNAs; miRNAs: microRNAs; lncRNAs: long non-coding RNAs; circRNAs: circular RNAs; MREs: microRNA response elements.