MicroRNA-148a Regulates Low-Density Lipoprotein Metabolism by Repressing the (Pro)renin Receptor

Authors

Na Wang, Shenzhen University, China
Lishu He, Medical College of Wisconsin
Hui Lin, Shenzhen University, China
Lunbo Tan, Shenzhen University, China
Yuan Sun, Shenzhen University, China
Xiaoying Zhang, Shenzhen University, China
A. H. Jan Danser, Rotterdam University, The Netherlands
Hong S. Lu, University of KentuckyFollow
Yongcheng He, Shenzhen Hengsheng Hospital, China
Xifeng Lu, Shenzhen University, China

Abstract

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR mRNA. Mutating the binding sites for miR-148a in the 3’-UTR of (P)RR mRNA completely abolished the inhibitory effects of miR-148a on (P)RR expression. In line with our recent findings, reduced (P)RR expression resulted in decreased cellular LDL uptake, likely as a consequence of decreased LDLR protein abundance. Overexpressing the (P)RR prevented miR-148a-induced reduction in LDLR abundance and cellular LDL uptake. Our study supports a new concept that miR-148a is a regulator of (P)RR expression. By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.

Document Type

Article

Publication Date

5-21-2020

Notes/Citation Information

Published in PLOS ONE, v. 15, no. 5, 0225356, p. 1-14.

© 2020 Wang et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0225356

Funding Information

This work is supported by National Natural Science Foundation of China (grant no. 81870605, 81800383, 81500667) and Shenzhen Municipal Science and Technology Innovation Council (grant no. JCYJ20160307160819191).

Repository Citation

Wang, Na; He, Lishu; Lin, Hui; Tan, Lunbo; Sun, Yuan; Zhang, Xiaoying; Danser, A. H. Jan; Lu, Hong S.; He, Yongcheng; and Lu, Xifeng, "MicroRNA-148a Regulates Low-Density Lipoprotein Metabolism by Repressing the (Pro)renin Receptor" (2020). Saha Cardiovascular Research Center Faculty Publications. 45.
https://uknowledge.uky.edu/cvrc_facpub/45