title: Paraquat inhibited differentiation in human neural progenitor cells (hNPCs) and down regulated miR-200a expression by targeting CTNNB1.
abstract: Paraquat (PQ) exposure influences central nervous system and results in serious neurotoxicity in vitro and in vivo. However, the role of PQ exposure in the development of CNS remains unclear. In present study, we investigated microRNAs (miRNAs) expression profiling and cell differential status following PQ treatment in human neural progenitor cells (hNPCs) as well as involved mechanism. Microarray profiling of miRNAs expression of PQ treated cell line and their corresponding control was determined. Differentially expression miRNAs were confirmed by quantitative real time PCR. Neural cell differentiation was performed with immunocytochemical analysis. Predicated target of miRNA was identified with luciferase reports and quantitatively analyzed using western blotting. Our results found PQ dramatically suppressed neural cell differentiation ability. 43 differentially expressed miRNAs were identified in PQ treated cells. The expression levels were over expressed in 25 miRNAs, whereas 18 miRNAs were suppressed. More importantly, we observed that miR-200a expression level to be lower in PQ treated cells. Luciferase assay and protein expression results confirmed the direct binding effect between CTNNB1 and miR-200a following PQ exposure. Collectively, our data suggested that down regulation of miR-200a in the PQ treated neural stem cell significantly participated in the differentiation processes and subsequently resulting in decreased cell viability, increased epithelial-mesenchymal transition process and the inhibited differential through CTNNB1 pathway.
authors.affiliation: The Department of Occupational and Environment Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan 750004, People's Republic of China. Electronic address: professorhungmin@tom.com.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lou
authors.affiliation: The Department of Occupational and Environment Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan 750004, People's Republic of China.
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: The Department of Occupational and Environment Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan 750004, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: The Department of Occupational and Environment Health, School of Public Health, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan 750004, People's Republic of China.
authors.forename: Hong-hui
authors.initials: HH
authors.lastname: Li
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010269:Paraquat / Q000633:toxicity*; D013234:Stem Cells; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D006540:Herbicides; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D010269:Paraquat
keywords: CTNNB1; Differentiation; MicroRNA array; Neurotoxicity; Paraquat; hNPCs