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Int. J. Mol. Sci. 2014, 15(10), 18422-18436; doi:10.3390/ijms151018422

Characterization of Paraquat-Induced miRNA Profiling Response in hNPCs Undergoing Proliferation

1,2,†
,
1,3,†
,
2
,
1
,
1
and
1,*
1
School of Public Health/MOE Key Lab of Public Health Safety/WHO Collaborating Center for Occupational Health, Fudan University, Shanghai 200032, China
2
Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, Yinchuan 750000, China
3
Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 21 August 2014 / Revised: 26 September 2014 / Accepted: 29 September 2014 / Published: 13 October 2014
(This article belongs to the Section Molecular Toxicology)
View Full-Text   |   Download PDF [3756 KB, uploaded 16 October 2014]   |  

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. View Full-Text
Keywords: paraquat; hNPCs; miRNA profiling; developmental neurotoxicity; target genes; biological processes; pathways paraquat; hNPCs; miRNA profiling; developmental neurotoxicity; target genes; biological processes; pathways
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Huang, M.; Lou, D.; Cai, Q.; Chang, X.; Wang, X.; Zhou, Z. Characterization of Paraquat-Induced miRNA Profiling Response in hNPCs Undergoing Proliferation. Int. J. Mol. Sci. 2014, 15, 18422-18436.

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