LINC01235-TWIST2 feedback loop facilitates epithelial–mesenchymal transition in gastric cancer by inhibiting THBS2

Abstract

Although the anomalous expression of long non-coding RNAs (lncRNAs) has been extensively investigated in numerous carcinomas including gastric cancer (GC), their function remains unclear. The aim of our study was to explore the role of LINC01235 in GC. We used real-time quantitative PCR (RT-qPCR) to measure the expression of LINC01235 and twist family bHLH transcription factor 2 (TWIST2) in GC tissues. Scratch and transwell assays were performed to evaluate cellular capacity for migration and invasion. Gene relationships were explored by Weighted Gene Co-Expression Network Analysis (WGCNA). We measured TWIST2, thrombospondin 2 (THBS2) and epithelial-mesenchymal transition (EMT)-related proteins with western blot. We also used Pearson correlation analysis and the Kaplan-Meier method to detect associations among genes and overall survival. We found that LINC01235 was upregulated in GC tissues and cells. LINC01235 down-regulation restricted migration and invasion. Interestingly, we found the LINC01235-TWIST2-THBS2 axis induced EMT. Additionally, TWIST2 upregulated LINC01235 transcription in luciferase and chromatin immunoprecipitation (ChIP) assays. Bioinformatics analysis showed that microRNA (miR)-6852-5p might be a key gene involved in the regulation of TWIST2 by LINC01235. The LINC01235-TWIST2 positive feedback loop mainly affected migration and invasion of GC cells, which suggests it may serve as a potential therapeutic target in gastric cancer.