C-Myc-activated intronic miR-210 and lncRNA MIR210HG synergistically promote the metastasis of gastric cancer. (1st February 2022)

• Record Type: Journal Article
• Authors: Li, Zhi-Yong; Xie, Ying; Deng, Mingxia; Zhu, Leqing; Wu, Xiaobin; Li, Guangqiang; Shi, Nan-Xi; Wen, Chuangyu; Huang, Weicai; Duan, Yuanyuan; Yin, Zhinan; Lin, Xue-Jia
• Is Part Of: Cancer letters. Volume 526(2022)
• Page Start: 322
• Page End: 334
• Publication Date: 2022-02-01
• Subjects: microRNA-210 -- MIR210HG -- Synergistic function -- Transcriptional regulation -- Metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.11.006
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The relationship between microRNA (miRNA) and hosting long non-coding RNA (lncRNA) remains unclear. Here, the expression levels of microRNA-210 (miR-210) and hosting lncRNA MIR210HG are significantly increased and positively correlated in gastric cancer (GC). Gain- and loss-of-function studies demonstrate that miR-210 and MIR210HG synergistically promote the migration and invasion of GC cells in vitro . Furthermore, GC sublines simultaneously expressing miR-210 and MIR210HG display synergistic promotion of lung metastasis in vivo . Mechanistically, MIR210HG interacts with DExH-box helicase 9 (DHX9) to increase DHX9/c-Jun complex's occupancy on the promoter of matrix metallopeptidases (MMPs), and thus promotes migration and invasion of GC cells. Additionally, miR-210 directly suppresses the expression of dopamine receptor D5 (DRD5), serine/threonine kinase 24 (STK24) and MAX network transcriptional repressor (MNT), resulting in enhanced migration and invasion. Finally, MYC proto-oncogene (c-Myc) transactivates miR-210 and MIR210HG. Overexpression of miR-210 or/and MIR210HG can rescue the inhibitory effect on the migration and invasion by silencing c-Myc. Moreover, c-Myc inhibitor significantly decreases lung metastasis of GC in vivo . Collectively, our findings identify a novel mechanism, by which c-Myc-activated miR-210 and MIR210HG synergistically promote the metastasis of GC. Highlights: Elucidate the functional association of miRNA and lncRNA in gastric cancer. Explore the mechanism of synergetic promotion by miR-210 and MIR210HG. Targeting c-Myc–miR-210/MIR210HG axis represents a potential therapeutic strategy.