Network of MicroRNAs Mediate Translational Repression of Bone Morphogenetic Protein Receptor-2: Involvement in HIV-Associated Pulmonary Vascular Remodeling

Journal of the American Heart Association
Mahendran ChinnappanNavneet K Dhillon

Abstract

Earlier, we reported that the simultaneous exposure of pulmonary arterial smooth muscle cells to HIV proteins and cocaine results in the attenuation of antiproliferative bone morphogenetic protein receptor-2 (BMPR2) protein expression without any decrease in its mRNA levels. Therefore, in this study, we aimed to investigate the micro RNA-mediated posttranscriptional regulation of BMPR2 expression. We identified a network of BMPR2 targeting micro RNAs including miR-216a to be upregulated in response to cocaine and Tat-mediated augmentation of oxidative stress and transforming growth factor-β signaling in human pulmonary arterial smooth muscle cells. By using a loss or gain of function studies, we observed that these upregulated micro RNAs are involved in the Tat- and cocaine-mediated smooth muscle hyperplasia via regulation of BMPR2 protein expression. These in vitro findings were further corroborated using rat pulmonary arterial smooth muscle cells isolated from HIV transgenic rats exposed to cocaine. More importantly, luciferase reporter and in vitro translation assays demonstrated that direct binding of novel miR-216a and miR-301a to 3'UTR of BMPR2 results in the translational repression of BMPR2 without any degradation of it...Continue Reading

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Citations

Sep 21, 2018·AIDS·Zachery J HarterNavneet K Dhillon
Oct 11, 2019·Physiological Reviews·Sushma K CribbsAlison Morris
Aug 29, 2018·International Journal of Molecular Sciences·Adam Andruska, Edda Spiekerkoetter
Aug 7, 2019·Journal of Experimental & Clinical Cancer Research : CR·Ziqiang ZhangJianjun Du
Nov 20, 2019·Heart Failure Reviews·Qi JinZhihong Liu

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Methods Mentioned

BETA
ubiquitination
in vitro transcription
transfection
Assay
PCR
transfections
transgenic

Software Mentioned

ImageJ
GraphPad prism
TargetScan

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