Linc00299/miR-490-3p/AURKA axis regulates cell growth and migration in atherosclerosis

Heart Vessels. 2019 Aug;34(8):1370-1380. doi: 10.1007/s00380-019-01356-7. Epub 2019 Feb 8.

Abstract

Long non-coding RNA (lncRNA) plays a crucial role in regulating various cellular processes in atherosclerosis. The present study identified the regulation of Linc00299, via miR-490-3p targeting Aurora kinase A (AURKA), on migration and proliferation of endothelial cells and vascular smooth muscle cells (VSMCs) during atherosclerosis. The expression of RNAs was assessed by real-time PCR. The proliferation, apoptosis and migration were detected using MTT assay, Annexin V/PI staining and Transwell system, respectively. Bindings of Linc00299/miR-490-3p and subsequent miR-490-3p/AURKA were verified by luciferase and biotin pull-down assays. The protein expression of AURKA was detected by Western blotting. Expressions of Linc00299 and miR-490-3p were upregulated and downregulated in atherosclerosis patients, respectively. Both Linc00299 knockdown and miR-490-3p overexpression suppressed cell proliferation, increased apoptosis and inhibited migration of VSMCs and HUVECs. Linc00299 directly bound to miR-490-3p which targeted AURKA. The regulation of Linc00299 on expression of AURKA and proliferation and migration of VSMCs were dependent on miR-490-3p. Atherosclerosis-increased Linc00299 acts as a sponge of miR-490-3p to upregulate AURKA, and as a result increases proliferation and migration in VSMCs and HUVECs. Our study reveals an important effect of Linc00299/miR-490-3p/AURKA axis on regulating cell proliferation and migration in atherosclerosis.

Keywords: AURKA; Atherosclerosis; Linc00299; Vascular smooth muscle cells; miR-490-3p.

MeSH terms

  • Apoptosis
  • Atherosclerosis / genetics*
  • Atherosclerosis / pathology
  • Aurora Kinase A / genetics*
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation
  • Endothelial Cells / cytology
  • Humans
  • MicroRNAs / genetics*
  • Myocytes, Smooth Muscle / cytology
  • RNA, Long Noncoding / genetics*
  • Up-Regulation

Substances

  • MIRN490 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • AURKA protein, human
  • Aurora Kinase A