LncRNA GAS5 acts as a ceRNA for miR-21 in suppressing PDGF-bb-induced proliferation and migration in vascular smooth muscle cells.

Abstract

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.