MicroRNA Alteration in Developing Rat Oligodendrocyte Precursor Cells Induced by Hypoxia-Ischemia

缺氧缺血诱导大鼠少突胶质细胞前体细胞发育过程中microRNA的变化

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作者:Xiaojuan Su, Dongqiong Xiao, Lingyi Huang, Shiping Li, Junjie Ying, Yu Tong, Qianghua Ye, Dezhi Mu, Yi Qu

Abstract

microRNAs (miRNAs) are involved in the pathogenesis of white matter injury (WMI). However, their roles in developing rat brains under hypoxia-ischemia (HI) insult remain unknown. Here, we examined the expression profiles of miRNAs in oligodendrocyte precursor cells using microarray analysis. We identified 162 miRNAs and only 6 were differentially regulated in HI compared with sham. Next, we used these 6 miRNAs and 525 extensively changed coding genes (fold change absolute: FC(abs) ≥2, p < 0.05) to establish the coexpression network, the result revealed that only 3 miRNAs (miR-142-3p, miR-466b-5p, and miR-146a-5p) have differentially expressed targeted mRNAs. RT-PCR analysis showed that the expression of the miRNAs was consistent with the microarray analysis. Further gene ontology and KEGG pathway analysis of the targets of these 3 miRNAs indicated that they were largely associated with neural activity. Furthermore, we found that 2 of the 3 miRNAs, miR-142-3p, and miR-466b-5p, have the same target gene, Capn6, an antiapoptotic gene that is tightly regulated in the pathogenesis of neurological diseases. Collectively, we have shown that a number of miRNAs change in oligodendrocyte precursor cells in response to HI insult in developing brains, and miR-142-3p/miR-466b-5p/Capn6 pathway might affect the pathogenesis of WMI, providing us new clues for the diagnosis and therapy for WMI.

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