title: Characterization of paraquat-induced miRNA profiling response in hNPCs undergoing proliferation.
abstract: Aberration during the development of the central nervous system (CNS) due to environmental factors underlies a variety of adverse developmental outcomes. Paraquat (PQ) is a widely studied neurotoxicant that perturbs the normal structure/function of adult CNS. Yet, the impacts of PQ exposure on the developing CNS remain unclear. miRNAs represent a class of small non-coding RNA molecules involved in the regulation of neural development. Thus in the present study, we analyzed the impacts of PQ on the miRNome of human neural progenitor cells (hNPCs) during proliferation by using the Exiqon miRCURY™ LNA Array. A total of 66 miRNAs were identified as differentially expressed in proliferating hNPCs upon PQ treatment. miRTarBase prediction identified 1465 mRNAs, including several genes (e.g., nestin, sox1, ngn1) previously proved to be associated with the neural proliferation and differentiation, as target genes of PQ-induced differentially expressed miRNAs. The database for annotation, visualization and integrated discovery (DAVID) bioinformatics analysis showed that target genes were enriched in regulation of cell proliferation and differentiation, cell cycle and apoptosis as well as tumor protein 53 (p53), Wnt, Notch and mitogen-activated protein kinases (MAPK) signaling pathways (p < 0.001). These findings were confirmed by real-time RT-PCR. Based on our results we conclude that PQ-induced impacts on the miRNA profiling of hNPCs undergoing proliferation may underlie the developmental neurotoxicity of PQ.
authors.affiliation: School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China. clever_hmin@aliyun.com.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China. delicia.ldan@gmail.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Lou
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, Yinchuan 750000, China. caiqian1212@126.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China. xlchang@shmu.edu.cn.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chang
authors.affiliation: School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China. 12211020063@fudan.edu.cn.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China. zjzhou@fudan.edu.cn.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*
chemical_list: D006540:Herbicides; D035683:MicroRNAs; D010269:Paraquat