title: miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4.
abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3'UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.
authors.affiliation: Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Yan
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D051858:Forkhead Transcription Factors; D006801:Humans; D035683:MicroRNAs / Q000494:pharmacology*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; C547665:MIRN421 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors