LncRNA TNK2-AS1 regulated ox-LDL-stimulated HASMC proliferation and migration via modulating VEGFA and FGF1 expression by sponging miR-150-5p

J Cell Mol Med. 2019 Nov;23(11):7289-7298. doi: 10.1111/jcmm.14575. Epub 2019 Aug 29.

Abstract

Long non-coding RNAs (lncRNAs) have been indicated for the regulatory roles in cardiovascular diseases. This study determined the expression of lncRNA TNK2 antisense RNA 1 (TNK2-AS1) in oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic smooth muscle cells (HASMCs) and examined the mechanistic role of TNK2-AS1 in the proliferation and migration of HASMCs. Our results demonstrated that ox-LDL promoted HASMC proliferation and migration, and the enhanced proliferation and migration in ox-LDL-treated HASMCs were accompanied by the up-regulation of TNK2-AS1. In vitro functional studies showed that TNK2-AS1 knockdown suppressed cell proliferation and migration of ox-LDL-stimulated HASMCs, while TNK2-AS1 overexpression enhanced HASMC proliferation and migration. Additionally, TNK2-AS1 inversely regulated miR-150-5p expression via acting as a competing endogenous RNA (ceRNA), and the enhanced effects of TNK2-AS1 overexpression on HASMC proliferation and migration were attenuated by miR-150-5p overexpression. Moreover, miR-150-5p could target the 3' untranslated regions of vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) to regulate FGF1 and VEGFA expression in HASMCs, and the inhibitory effects of miR-150-5p overexpression in ox-LDL-stimulated HASMCs were attenuated by enforced expression of VEGFA and FGF1. Enforced expression of VEGFA and FGF1 also partially restored the suppressed cell proliferation and migration induced by TNK2-AS1 knockdown in ox-LDL-stimulated HASMCs, while the enhanced effects of TNK2-AS1 overexpression on HASMC proliferation and migration were attenuated by the knockdown of VEGFA and FGF1. Collectively, our findings showed that TNK2-AS1 exerted its action in ox-LDL-stimulated HASMCs via regulating VEGFA and FGF1 expression by acting as a ceRNA for miR-150-5p.

Keywords: TNK2-AS1; fibroblast growth factor 1; human aortic smooth muscle cells; miR-150-5p; proliferation and migration; vascular endothelial growth factor A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblast Growth Factor 1 / genetics
  • Fibroblast Growth Factor 1 / metabolism*
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Oligonucleotides, Antisense / genetics
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics
  • RNA, Long Noncoding / genetics*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Lipoproteins, LDL
  • MIRN150 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Long Noncoding
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • oxidized low density lipoprotein
  • Fibroblast Growth Factor 1
  • Protein-Tyrosine Kinases
  • TNK2 protein, human