title: 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.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.|Harvard T.H. Chan School of Public Health, Boston, MA, 02115, U.S.A.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, MA, 02115, U.S.A.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Kaiyi
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Regenerative Medicine and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, 20000, P.R. China.
authors.forename: Ruixuan
authors.initials: R
authors.lastname: Geng
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Congqi
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Jinjia
authors.initials: J
authors.lastname: Chang
authors.affiliation: International Medical Services, Peking Union Medical College Hospital, Beijing, 100000, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Medical Oncology, Fudan University, Shanghai Cancer Center, Shanghai, 200000, P.R. China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200000, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D015820:Cadherins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C547665:MIRN421 microRNA, human; D035683:MicroRNAs; D053148:Caspase 3; D002945:Cisplatin
keywords: HIF-1α; cisplatin resistance; epithelial-mesenchymal transition; gastric cancer; miR-421