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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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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