c-Myc-activated intronic miR-210 and lncRNA MIR210HG synergistically promote the metastasis of gastric cancer

作者：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^*

来源：Cancer Letters, 2022, 526: 322-334.

DOI：10.1016/j.canlet.2021.11.006

• microRNA-210
• MIR210HG
• Synergistic function
• Transcriptional regulation
• Metastasis

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.

• 单位
  中山大学; 6; 南方医科大学