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

Abstract	Hypoxia and dysregulation of microRNAs (miRNAs) have been identified as crucial factors in carcinogenesis. However, the potential mechanisms of HIF-1α and miR-421 in gastric cancer have not been well elucidated. In this study, we found that miR-421 was up-regulated by HIF-1α. 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.
Authors	Xiaoxiao Ge, Xinyang Liu, Fengjuan Lin, Peng Li, Kaiyi Liu, Ruixuan Geng, Congqi Dai, Ying Lin, Wenbo Tang, Zheng Wu, Jinjia Chang, Jianwei Lu, Jin Li
Journal	Oncotarget (Oncotarget) Vol. 7 Issue 17 Pg. 24466-82 (Apr 26 2016) ISSN: 1949-2553 [Electronic] United States
PMID	27016414 (Publication Type: Journal Article)
Chemical References	3' Untranslated Regions Antineoplastic Agents Cadherins Hypoxia-Inducible Factor 1, alpha Subunit MIRN421 microRNA, human MicroRNAs Caspase 3 Cisplatin
Topics	3' Untranslated Regions (genetics) Animals Antineoplastic Agents (pharmacology) Apoptosis (drug effects, genetics) Cadherins (genetics, metabolism) Caspase 3 (genetics, metabolism) Cell Line, Tumor Cisplatin (pharmacology) Drug Resistance, Neoplasm (drug effects, genetics) Female Gene Expression Regulation, Neoplastic Humans Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism) Kaplan-Meier Estimate Male Mice, Inbred BALB C Mice, Nude MicroRNAs (genetics) Middle Aged Neoplasm Metastasis Prognosis RNA Interference Stomach Neoplasms (drug therapy, genetics, metabolism) Xenograft Model Antitumor Assays

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