MicroRNA-421 regulated by HIF-1α promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer

作者：Ge, Xiaoxiao; Liu, Xinyang; Lin, Fengjuan; Li, Peng; Liu, Kaiyi; Geng, Ruixuan; Dai, Congqi; Lin, Ying; Tang, Wenbo; Wu, Zheng; Chang, Jinjia; Lu, Jianwei^*; Li, Jin^*

来源：Oncotarget, 2016, 7(17): 24466-24482.

DOI：10.18632/oncotarget.8228

• gastric cancer
• miR-421
• HIF-1 alpha
• cisplatin resistance
• epithelial-mesenchymal transition

Hypoxia and dysregulation of microRNAs (miRNAs) have been identified as crucial factors in carcinogenesis. However, the potential mechanisms of HIF-1 alpha and miR-421 in gastric cancer have not been well elucidated. In this study, we found that miR-421 was up-regulated by HIF-1 alpha. Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer in vivo and in vitro. E-cadherin and caspase-3 were identified as targets of miR-421. Besides, relative mRNA expression of miR-421 was significantly increased in gastric cancer tumor tissues compared with non-tumor tissues in a cohort of gastric cancer specimens (n=107). The expression of miR-421 was higher in advanced gastric cancers compared with localized ones. Moreover, Kaplan-Meier analysis illustrated that those patients with low levels of miR-421 had a significant longer overall survival (p = 0.006) and time to relapse (p = 0.007). Therefore, miR-421 could serve as an important prognostic marker and a potential molecular target for therapy in gastric cancer.

• 出版日期2016-4-26
• 单位北京协和医学院; 中国医学科学院北京协和医院; 复旦大学; 同济大学