HDAC3-Mediated Repression of LncRNA-LET Regulates Gastric Cancer Cell Growth Proliferation, Invasion, Migration, and Apoptosis via MiR-548k.

Abstract

Emerging studies have indicated the aberrant expression of histone deacetylases (HDACs) is closely associated with the development of tumors. However, the regulatory roles of HDACs-regulated long noncoding RNAs (lncRNA) in gastric cancer (GC) remain largely unknown. In this study, the effects of HDAC3 and HDAC3-mediated lncRNA-LET on the progression of GC were investigated. The expressions of HDAC3, lncRNA-LET, and miR-548k in GC cell lines were analyzed. The biological functions of HDAC3 and lncRNA-LET were measured by CCK-8 assay, Transwell assay, Western blot analysis, and cell apoptosis assays. Chromatin immunoprecipitation and luciferase reporter assay verified the regulatory relationship between HDAC3 and lncRNA-LET, and lncRNA-LET and miR-548 in GC cells. HDAC3 was significantly overexpressed in GC cell lines compared to GES-1. Knockdown of HDAC3 suppressed the proliferation, invasion, and migration of AGS and SGC-7901 cells, while cell apoptosis was promoted. Silenced HDAC3 promoted histone acetylation in the promoter region of lncRNA-LET, subsequently upregulating the expression of lncRNA-LET in AGS and SGC-7901 cells. In addition, overexpressed lncRNA-LET notably inhibited the proliferation, invasion, and migration of GC cells, whereas apoptosis was enhanced. LncRNA-LET could function as the sponge of miR-548k. HDAC3 was able to regulate the progression of GC cells via the lncRNA-LET/miR-548k signaling pathway. We confirmed that the HDAC3/lncRNA-LET/miR-548k signal axis mediated the occurrence and development of GC, and HDAC3 could be a novel therapeutic target for the treatments of GC.