Long non-coding RNA GAS5 knockdown facilitates proliferation and impedes apoptosis by regulating miR-128-3p/FBLN2 axis in ox-LDL-induced THP-1 cells

Abstract

BACKGROUND: Long non-coding RNAs (lncRNAs) are found to involve in modulating the development of atherosclerosis (AS). But the molecular mechanism of lncRNA growth-arrest specific transcript 5 (GAS5) in AS is not fully understood. METHODS: QRT-PCR was performed to measure the abundances of GAS5, miR-128-3p and fibulin 2 (FBLN2). Oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells were employed as cell models of AS. The cell proliferation and apoptosis were analyzed using CCK-8 and Flow cytometry assays, respectively. Levels of all protein were examined by western blot. The interaction among GAS5, miR-128-3p and FBLN2 was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: GAS5 was elevated and miR-128-3p was decreased in the serum of patients with AS and ox-LDL-stimulated THP-1 cells. Ox-LDL stimulation inhibited proliferation and induced apoptosis of THP-1 cells. Meanwhile, GAS5 directly targeted miR-128-3p and inversely modulated its expression. Importantly, GAS5 depletion facilitated cell proliferation and impaired apoptosis in ox-LDL-induced THP-1 cells. Additionally, GAS5 augmented FBLN2 expression through sponging miR-128-3p, and miR-128-3p facilitated proliferation and retarded apoptosis of ox-LDL-induced THP-1 cells by targeting FBLN2. CONCLUSION: GAS5 knockdown promoted the growth of ox-LDL-induced THP-1 cells through down-modulating FBLN2 and increasing miR-128-3p, suggesting the potential value of GAS5 for treatment of AS.