Characterization of paraquat-induced miRNA profiling response in hNPCs undergoing proliferation.
Characterization of paraquat-induced miRNA profiling response in hNPCs undergoing proliferation.
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百草枯诱导的 hNPC 增殖中 miRNA 分析响应的表征
DOI：
10.3390/ijms151018422
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发表时间：
2014-10-13
影响因子：
5.6
通讯作者：
Zhou Z
中科院分区：
文献类型：
--
作者：
Huang M;Lou D;Cai Q;Chang X;Wang X;Zhou Z
中枢神经系统（CNS）发育过程中由于环境因素引起的畸变是各种不良发育结果的基础。百草枯（Paraquat，PQ）是一种被广泛研究的神经毒物，可干扰成年人中枢神经系统的正常结构和功能。然而，PQ暴露对发育中的CNS的影响仍不清楚。miRNAs是一类参与神经发育调控的非编码RNA小分子。因此，在本研究中，我们通过使用微阵列miRCURY™ LNA阵列分析了PQ对人神经祖细胞（hNPC）增殖期间miRNome的影响。共鉴定出66种miRNA在PQ处理后增殖的hNPC中差异表达。miRTarBase预测鉴定了1465个mRNA，包括几个基因（例如，nestin，sox 1，ngn 1）作为PQ诱导的差异表达miRNAs的靶基因，与神经细胞的增殖和分化有关。大卫数据库生物信息学分析显示，靶基因在细胞增殖分化、细胞周期和凋亡调控以及肿瘤蛋白53（p53）、Wnt、Notch和丝裂原活化蛋白激酶（MAPK）信号通路中富集（p < 0.001）。这些发现通过实时RT-PCR得到证实。基于我们的研究结果，我们得出结论，PQ诱导的影响的miRNA谱的hNPC进行增殖可能是潜在的发育神经毒性的PQ。
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.
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影响因子：
48
作者：
Grandjean, Philippe;Landrigan, Philip J.
通讯作者：
Landrigan, Philip J.
影响因子：
5.1
作者：
Djukic, Mirjana M.;Jovanovic, Marina D.;Vekic, Jelena
通讯作者：
Vekic, Jelena
影响因子：
5.3
作者：
Meza-Sosa KF;Pedraza-Alva G;Pérez-Martínez L
通讯作者：
Pérez-Martínez L
影响因子：
9.9
作者：
Liou, HH;Tsai, MC;Chen, RC
通讯作者：
Chen, RC
影响因子：
3.4
作者：
Davoodian, Nahid;Lotfi, Abbas S.;Arjmand, Sare
通讯作者：
Arjmand, Sare