title: MicroRNA-191, by promoting the EMT and increasing CSC-like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells.
abstract: Lung cancer is the leading cause of cancer mortality worldwide. A common interest in lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence that microRNAs (miRNAs) are involved in lung cancer. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and lung cancer, we analyzed miRNA expression profiles of human bronchial epithelial (HBE) cells malignantly transformed by arsenite. High-throughput microarray analysis showed that 51 miRNAs were differentially expressed in transformed HBE cells relative to normal HBE cells. In particular, miR-191 was up-regulated in transformed cells. In HBE cells, arsenite induced increases of miR-191 and WT1 levels, decreased BASP1 expression, and activated the Wnt/β-catenin pathway, effects that were blocked by miR-191 knockdown. In addition, a luciferase reporter assay indicated that BASP1 is a direct target of miR-191. By inhibiting the expression of BASP1, miR-191 increased the expression of WT1 to promote activation of Wnt/β-catenin pathway. In transformed cells, inhibition of miR-191 expression blocked the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of cells and decreased their migratory capacity and neoplastic properties. Thus, these results demonstrate that miR-191 modulates the EMT and the CSC-like properties of transformed cells and indicate that it is an onco-miR involved in the neoplastic and metastatic properties of transformed cells.
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xu
authors.affiliation: The First Clinic Medical College, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ji
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Bairu
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D001984:Bronchial Neoplasms / Q000235:genetics / Q000473:pathology*; D002461:Cell Line, Transformed; D017931:DNA Primers; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C546177:MIRN191 microRNA, human; D035683:MicroRNAs
keywords: Wilms' tumor protein (WT1); Wnt/β-catenin signaling; cancer stem cells (CSCs); epithelial-mesenchymal transition (EMT); miR-191