School of Basic Medical Sciences, Xiangnan University, Chenzhou, P.R. China.
Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
J Cell Biochem. 2019 Sep;120(9):15233-15240. doi: 10.1002/jcb.28789. Epub 2019 May 8.
Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute significantly to the development of many human cardiovascular diseases, including hypertension. The present study aimed to evaluate the in vitro functional roles of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in VSMCs and explored the underlying molecular mechanisms. We found that GAS5 was significantly downregulated in PDGF-bb-treated VSMCs, and overexpression of GAS5 remarkably attenuated PDGF-bb-induced VSMC proliferation and migration. In addition, miR-21 was observed to potentially bind to GAS5, and we also identified that PDCD4 might be a direct target of miR-21 in VSMCs. Cotransfection of miR-21 mimics remarkably reduced the PDCD4 protein expression in GAS5 overexpressing VSMCs. Further, rescue experiments showed that enforced expression of miR-21 attenuated the inhibitory effects of GAS5 on VSMC proliferation and migration. Collectively, our results demonstrated that GAS5 inhibits PDGF-bb-induced VSMC proliferation and migration, partly through acting as a competing endogenous RNA of miR-21, and provided new evidence that GAS5 may serve as a potential therapeutic target for hypertension.
血管平滑肌细胞(VSMCs)的异常增殖和迁移对许多人类心血管疾病的发展,包括高血压,有重要作用。本研究旨在评估长链非编码 RNA 生长停滞特异性转录物 5(GAS5)在 VSMCs 中的体外功能作用,并探讨其潜在的分子机制。我们发现,GAS5 在 PDGF-bb 处理的 VSMCs 中显著下调,GAS5 的过表达显著减弱了 PDGF-bb 诱导的 VSMC 增殖和迁移。此外,观察到 miR-21 可能与 GAS5 结合,并且我们还鉴定出 PDCD4 可能是 VSMCs 中 miR-21 的直接靶标。miR-21 模拟物的共转染显著降低了 GAS5 过表达 VSMCs 中的 PDCD4 蛋白表达。此外,挽救实验表明,miR-21 的强制表达减弱了 GAS5 对 VSMC 增殖和迁移的抑制作用。总之,我们的结果表明,GAS5 通过作为 miR-21 的竞争性内源性 RNA 来抑制 PDGF-bb 诱导的 VSMC 增殖和迁移,并提供了新的证据表明,GAS5 可能成为高血压的潜在治疗靶点。