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

Aging (Albany NY). 2020 Apr 13;12(7):5948-5976. doi: 10.18632/aging.102989. Epub 2020 Apr 13.

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.

Keywords: HOXA3; integrated bioinformatics analyses; miR-10a-5p; osteoarthritis; the whole transcriptome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Computational Biology
  • Disease Progression
  • Exome Sequencing / methods
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks
  • Homeodomain Proteins / genetics
  • Humans
  • MicroRNAs / genetics*
  • Osteoarthritis* / genetics
  • Osteoarthritis* / physiopathology
  • Pharmacogenetics / methods
  • Signal Transduction / genetics

Substances

  • HOXA3 protein, human
  • Homeodomain Proteins
  • MIRN10 microRNA, human
  • MicroRNAs