HDAC3-Mediated Repression of LncRNA-LET Regulates Gastric Cancer Cell Growth Proliferation, Invasion, Migration, and Apoptosis via MiR-548k
Jie Zhang, Xiaoyu Liu, Jun Chen, Shufeng Xia
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.