Circ-SATB2 upregulates STIM1 expression and regulates vascular smooth muscle cell proliferation and differentiation through miR-939

Biochem Biophys Res Commun. 2018 Oct 20;505(1):119-125. doi: 10.1016/j.bbrc.2018.09.069. Epub 2018 Sep 18.

Abstract

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved. More and more studies have found that circular RNAs (circRNAs) may play important roles in the development of CHD. Here detection of vascular smooth muscle cells (VSMCs) showed that circ-SATB2 and STIM1 were up-regulated in proliferative VSMCs, while miR-939 were down-regulated. Circ-SATB2 and miR-939 did not affect the expression of each other, but circ-SATB2 could promote while miR-939 inhibited the expression of STIM1 (a target gene of miR-939). Circ-SATB2 overexpression could inhibit the expression of SM22-alpha (SM22α, a marker of contractile VSMCs), while the expression of SM22α was promoted by miR-939. STIM1 could promote cell proliferation and migration, and circ-SATB2 had similar effects, but its linear sequence had no such functions. MiR-939 had the opposite effects, could promote cell apoptosis and inhibit cell proliferation and migration, and siRNAs targeting circ-SATB2 had similar effects. When co-transfected with circ-SATB2 over-expression vector and miR-939 mimics or STIM1 siRNAs, the changes of cell proliferation, apoptosis and migration were not significant. Therefore, circ-SATB2 can regulate VSMC phenotypic differentiation, proliferation, apoptosis and migration by promoting the expression of STIM1. This discovery will provide a theoretical reference for exploring the role of circRNA in VSMCs and the pathogenesis of CHD.

Keywords: Atherosclerosis; Coronary artery disease; Vascular smooth muscle cell; circRNA; miR-939.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation
  • Humans
  • Matrix Attachment Region Binding Proteins / genetics
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • RNA / genetics*
  • RNA Interference
  • RNA, Circular
  • Stromal Interaction Molecule 1 / genetics*
  • Stromal Interaction Molecule 1 / metabolism
  • Transcription Factors / genetics
  • Up-Regulation

Substances

  • MIRN939 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • Microfilament Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • RNA, Circular
  • SATB2 protein, human
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Transcription Factors
  • transgelin
  • RNA