BTEB2-Activated lncRNA TSPEAR-AS2 Drives GC Progression through Suppressing GJA1 Expression and Upregulating CLDN4 Expression
Zhonghua Ma, You Shuai, Xiang-Yu Gao, Yan Yan, Ke‐Ming Wang, Xianzi Wen, Jiafu Ji
Abstract
using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment.