Silencing of GAS5 represses the malignant progression of atherosclerosis through upregulation of miR-135a.

Long non-coding RNA growth arrest-specific 5 (GAS5) has been demonstrated to be involved in the pathogenesis of atherosclerosis (AS). The purpose of the present study was to investigate the underlying mechanisms of GAS5 on the inflammation and lipid metabolic disorders of AS. ApoE mice were fed on a high fat diet (HFD) and THP-1 macrophages were treated with ox-LDL to construct AS model in vivo and in vitro, respectively. The detections of blood lipids and inflammatory cytokines were performed using corresponding assay kits. qRT-PCR was used to assess the expression of GAS5 and miR-135a. Western blot was performed to detect PPARα and CPT1 levels. The targeted interaction between GAS5 and miR-135a was determined by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our data revealed that GAS5 was upregulated in AS mice model and ox-LDL-treated macrophages. GAS5 silencing alleviated lipid metabolic disorders and inflammation in AS mice and ox-LDL-treated macrophages. Moreover, GAS5 directly targeted miR-135a and repressed miR-135a expression. MiR-135a expression restoration abrogated the alleviative effects of GAS5 silencing on inflammation and lipid metabolic disorders in ox-LDL-treated macrophages. In conclusion, our study suggested that GAS5 silencing repressed the malignant progression of AS at least partly through upregulation of miR-135a. Targeting GAS5 might be a promising treatment strategy for AS management.