• Neurobiology of disease · Mar 2014

    MiR-139-5p inhibits HGTD-P and regulates neuronal apoptosis induced by hypoxia-ischemia in neonatal rats.

    • Yi Qu, Jinlin Wu, Dapeng Chen, Fengyan Zhao, Junyan Liu, Chunlei Yang, Dapeng Wei, Donna M Ferriero, and Dezhi Mu.
    • Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, 610041 Chengdu, Sichuan, China. Electronic address: quyi712002@163.com.
    • Neurobiol. Dis. 2014 Mar 1; 63: 184-93.

    AbstractHuman growth transformation dependent protein (HGTD-P) is a newly identified protein that promotes neuronal apoptosis in hypoxia-ischemia brain damage (HIBD) in neonatal rats. However, the mechanisms regulating HGTD-P expression are not clear. Here we describe microRNAs targeted to HGTD-P and examine their effects on regulating neuronal apoptosis in HIBD. We use samples from cultured neurons after oxygen-glucose deprivation (OGD) and postnatal day 10 rat brains after hypoxia-ischemia (HI). RT-PCR, Western blotting, and immunostaining are used to detect the expression of HGTD-P and cleaved caspase 3, as well as real-time PCR detects microRNA expression. MicroRNA agomir is used to inhibit the expression of HGTD-P, and DAPI, TUNEL, and TTC staining are employed to detect cell apoptosis and brain damage. Moreover, in vitro processing assay is used to examine the mechanism by which HI down-regulates miR-139-5p expression. We found that miR-139-5p is down-regulated in neurons and rat brains after HI treatment. The expression pattern of miR-139-5p correlates inversely with that of HGTD-P. Furthermore, miR-139-5p agomir inhibits neuronal apoptosis and attenuates HIBD, which is concurrent with down-regulation of HGTD-P. Moreover, pre-miR-139 processing activity decreases in extracts from OGD neurons, and OGD neuronal extracts attenuates the processing of pre-miR-139 by Dicer. In conclusion, HI induces inhibitors which block the processing step of pre-miR-139, resulting in the down-regulation of mature miR-139-5p. The down-regulation of miR-139-5p plays a critical role in the up-regulation of HGTD-P expression. MiR-139-5p agomir attenuates brain damage when used 12h after HI, providing a longer therapeutic window than anti-apoptosis compounds currently available. Copyright © 2013 Elsevier Inc. All rights reserved.

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