An oncogenic lncRNA, GLCC1, promotes tumorigenesis in gastric carcinoma by enhancing the c-Myc/IGF2BP1 interaction

Dong-Liang Yang, Lin-Fei Dong, Yin-Bing Qiu,  Gen-Yan Luo

Abstract:

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) are vital regulators of the expression of various genes in multiple human diseases. The aim of this study was to investigate the role of glycolysis-associated lncRNA of colorectal cancer (GLCC1) in the progression of gastric carcinoma as well as the underlying mechanism. The expression levels of GLCC1 and c-Myc were determined in 47 pairs of gastric carcinoma tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). Next, the functional roles of GLCC1 and c-Myc in the proliferation, apoptosis, migration, and invasion of gastric carcinoma cells (BGC823 and SGC7901 cells) were determined by siRNA-mediated knockdown of these molecules, and the cells were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays. In addition, RIP and RNA pull-down assays were used to examine the interaction between GLCC1 and c-Myc/IGF2BP1. Further mechanistic studies were conducted using western blotting. lncRNA GLCC1 and c-Myc were observed to be significantly increased in both gastric carcinoma tissues and cell lines. Knockdown of GLCC1 or c-Myc suppressed cell proliferation, migration, and invasion but promoted apoptosis in both the BGC823 and SGC7901 cell lines. Mechanistically, c-Myc was identified as a downstream regulator involved in the GLCC1-mediated biological effects in gastric carcinoma. The RNA pull-down and RIP assays further showed that the upregulation of lncRNA GLCC1 enhanced the interaction of the IGF2BP1 protein with c-Myc mRNA, thus promoting the stabilization of c-Myc mRNA. Altogether, we demonstrated that lncRNA GLCC1 modulates gastric cancer cell migration and invasion by enhancing the c-Myc/IGF2BP1 interaction, and lncRNA GLCC1 may serve as a potential therapeutic target for preventing the development and progression of human gastric carcinoma.