title: MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4.
abstract: Previous studies have shown that dysregulation of microRNA-150 (miR-150) is associated with aberrant proliferation of human non-small cell lung cancer (NSCLC) cells. However, whether miR-150 has a critical role in NSCLC cell metastasis is unknown. Here, we reveal that the critical pro-metastatic role of miR-150 in the regulation of epithelial-mesenchymal-transition (EMT) through down-regulation of FOXO4 in NSCLC. In vitro, miR-150 targets 3'UTR region of FOXO4 mRNA, thereby negatively regulating its expression. Clinically, the expression of miR-150 was frequently up-regulated in metastatic NSCLC cell lines and clinical specimens. Contrarily, FOXO4 was frequently down-regulated in NSCLC cell lines and clinical specimens. Functional studies show that ectopic expression of miR-150 enhanced tumor cell metastasis in vitro and in a mouse xenograft model, and triggered EMT-like changes in NSCLC cells (including E-cadherin repression, N-cadherin and Vimentin induction, and mesenchymal morphology). Correspondingly, FOXO4 knockdown exhibited pro-metastatic and molecular effects resembling the effect of miR-150 over-expression. Moreover, NF-κB/snail/YY1/RKIP circuitry regulated by FOXO4 were likely involved in miR-150-induced EMT event. Simultaneous knockdown of miR-150 and FOXO4 abolished the phenotypic and molecular effects caused by individual knockdown of miR-150. Therefore, our study provides previously unidentified pro-metastatic roles and mechanisms of miR-150 in NSCLC.
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Respiratory Disease Research Institute, Second XiangYa Hospital of Central South University, Changsha, 410011, China.
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Ouyang
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Ye
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 400083, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, 410078, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Feng
authors.affiliation: The State Key Laboratory of Medical Genetics &School of Life Sciences, Central South University, Changsha, 410078, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors; C108803:FOXO4 protein, human; C533097:MIR150, human