MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

Yan Zeng; Yanping Pan; Hongtai Liu; Kang Kang; Yike Wu; Gang Hui; Wenda Peng; Ramaswamy Ramchandran; J Usha Raj; Deming Gou

doi:10.1016/j.febslet.2014.10.040

MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

FEBS Lett. 2014 Dec 20;588(24):4677-85. doi: 10.1016/j.febslet.2014.10.040. Epub 2014 Nov 13.

Authors

Yan Zeng¹, Yanping Pan², Hongtai Liu², Kang Kang², Yike Wu², Gang Hui³, Wenda Peng⁴, Ramaswamy Ramchandran⁵, J Usha Raj⁵, Deming Gou⁶

Affiliations

¹ Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China.
² Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
³ Department of Chest Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, China.
⁴ Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China.
⁵ Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA.
⁶ Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China; Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: dmgou@szu.edu.cn.

PMID: 25447536
DOI: 10.1016/j.febslet.2014.10.040

Abstract

Chronic hypoxia triggers pulmonary vascular remodeling, which is associated with de-differentiation of pulmonary artery smooth muscle cells (PASMC). Here, we show that miR-20a expression is up-regulated in response to hypoxia in both mouse and human PASMC. We also observed that miR-20a represses the protein kinase, cGMP-dependent, type I (PRKG1) gene and we identified two crucial miR-20a binding sites within the coding region of PRKG1. Functional studies showed that miR-20a promotes the proliferation and migration of human PASMC, whereas it inhibits their differentiation. In summary, we provided a possible mechanism by which hypoxia results in decreased PRKG1 expression and in the phenotypic switching of PASMC.

Keywords: Coding region; Hypoxia; MicroRNA; Pulmonary arterial smooth muscle cells; cGMP-dependent protein kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cell Differentiation / genetics
Cell Hypoxia
Cell Movement / genetics
Cell Proliferation / genetics
Conserved Sequence
Cyclic GMP-Dependent Protein Kinase Type I / genetics*
Gene Expression Regulation, Enzymologic / genetics
Humans
Lung / metabolism
Mice
MicroRNAs / genetics*
Myocytes, Smooth Muscle / cytology
Myocytes, Smooth Muscle / metabolism*
Open Reading Frames / genetics*
Phenotype
Pulmonary Artery / cytology*

Substances

MIRN20a microRNA, human
MicroRNAs
Cyclic GMP-Dependent Protein Kinase Type I
PRKG1 protein, human
Prkg1 protein, mouse