[Alterations of miRNA profiles and function analysis in paraquat-induced apoptosis of hNPCs].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases

PubMedID: 28241697

Huang M, Cai Q, Li HH, Lou D. [Alterations of miRNA profiles and function analysis in paraquat-induced apoptosis of hNPCs]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017;35(1):19-24.
OBJECTIVE
To investigate the impacts of paraquat on microRNA profiles in apoptosis of human neural progenitor cells (hNPCs) and to explore miRNA targets and biological functions.

METHODS
We used hNPCs as a popular in vitro cell model system for characterizing the neurotoxicity.Cell apoptosis was detected by Annexin V-APC/7-AAD after 24 h treatment with different concentrations of PQ (0, 5, 10, 20, 40, 80 µmol/L). Microarray profiling expression of PQ treated cell line and their corresponding control was determined and differentially expression miRNAs were confirmed by quantitatively real-time PCR. The target genes regulated by aberrantly expressed miRNAs were predicted by on line-available software (Target Scan, Miranda, Mirbase). The GO and KEGG pathway database were used to analyze the functions of target genes. Meanwhile, the apoptosis-related protein expressions were evaluated by western blot.

RESULTS
cell apoptosis increased with increasing PQ concentrations (from 10 to 80µmol/L) in a dose-dependent manner (P<0.05). miRNA microarray showed that 40 miRNAs were significantly up-regulated while 26 miRNAs were down-regulated after 20 µmol/L PQ treatment (P< 0. 05). We selected 6 differentially expressed miRNAs to validate with qRT-PCR.

THE RESULTS
were consistent with microarray data for all miRNAs tested.Bioinformatics analysis demonstrated target genes were enriched in regulation of neuron apoptosis and differentiation, MARK signaling pathway as well as P53 signaling pathway. The protein expressions of bax and caspase3 significantly increased while bcl-2 significantly decreased treated with PQ compared with control group (P<0. 05).

CONCLUSION
There is a specific miRNA expression profile in paraquat-induced apoptosis of hNPCs.Differentially expression miRNAs regulated apoptosis of hNPCs through multiple molecular signaling pathways and especially for mitochondrial apoptosis pathway.