Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Department of Cardiology, The Affiliated Hospital of Yan'an University, Yan'an 716000, China.
Department of Cardiology, The Affiliated Hospital of Yan'an University, Yan'an 716000, China.
Biochem Biophys Res Commun. 2018 Oct 20;505(1):119-125. doi: 10.1016/j.bbrc.2018.09.069. Epub 2018 Sep 18.
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.
冠心病（CHD）的防治是一个亟待解决的难题。越来越多的研究发现环状 RNA（circRNAs）可能在 CHD 的发生发展中发挥重要作用。本研究检测血管平滑肌细胞（VSMCs）发现，增殖性 VSMCs 中circ-SATB2 和 STIM1 上调，而 miR-939 下调。circ-SATB2 和 miR-939 彼此不影响表达，但 circ-SATB2 可促进而 miR-939 抑制 STIM1（miR-939 的靶基因）的表达。circ-SATB2 过表达可抑制收缩型 VSMCs 标志物 SM22-α（SM22α）的表达，而 miR-939 则促进 SM22α 的表达。STIM1 可促进细胞增殖和迁移，circ-SATB2 具有类似作用，但线性序列无此功能。miR-939 则相反，可促进细胞凋亡，抑制细胞增殖和迁移，靶向 circ-SATB2 的 siRNAs 也具有类似作用。当共转染 circ-SATB2 过表达载体和 miR-939 模拟物或 STIM1 siRNAs 时，细胞增殖、凋亡和迁移的变化不明显。因此，circ-SATB2 可通过促进 STIM1 的表达来调节 VSMC 表型分化、增殖、凋亡和迁移。这一发现将为探索 circRNA 在 VSMCs 中的作用和 CHD 的发病机制提供理论参考。
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