Format

Send to

Choose Destination
Cardiovasc Res. 2015 Sep 1;107(4):534-45. doi: 10.1093/cvr/cvv160. Epub 2015 May 29.

MicroRNA-1298 is regulated by DNA methylation and affects vascular smooth muscle cell function by targeting connexin 43.

Author information

1
Division of Vascular Surgery, The Guangdong Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The Vascular Surgical Disease Research Center of Guangdong Province, First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, Guangdong 510080, China.
2
Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
3
Division of Vascular Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
4
Department of Pharmacology, Rush University Medical Center, Chicago, USA.
5
Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
6
Division of Vascular Surgery, The Guangdong Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The Vascular Surgical Disease Research Center of Guangdong Province, First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, Guangdong 510080, China 13922231628@163.com shenmingwang@hotmail.com.

Abstract

AIMS:

Growing evidence links microRNA to the process of peripheral vascular disease. Recently, we have found that microRNA-1298(miR-1298) is one of the most significantly down-regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, little is known regarding its role in the process of ASO. The present study aimed to investigate the expression, regulatory mechanisms, and functions of miR-1298 in the process of ASO.

METHODS AND RESULTS:

Using quantitative reverse-transcription PCR and in situ hybridization assays, miR-1298 was observed predominantly expressed in the vascular smooth muscle cells (VSMCs) and was significantly down-regulated in ASO compared with normal arteries. Pyrosequencing analysis revealed that the miR-1298 DNA upstream of CpG sites were hypermethylated in ASO compared with normal arteries. Next, the luciferase reporter assay revealed that miR-1298 down-regulation is related with upstream DNA CpG site hypermethylation. Introducing a miR-1298 mimic into cultured VSMCs significantly attenuated cell proliferation and migration. Connexin 43 (Cx43) was validated to be a functional target of miR-1298 that was involved in the miR-1298-mediated cellular effects. Finally, lentivirus-mediated delivery of miR-1298 and its target Cx43 into a rat carotid balloon injury model indicated that re-overexpression of miR-1298 significantly decreased neointimal formation by targeting connexin 43.

CONCLUSION:

Our data demonstrate a specific role of the upstream DNA methylation/miR-1298/Cx43 pathway in regulating VSMC function and suggest that modulation of miR-1298 levels may offer a novel therapeutic approach for ASO.

KEYWORDS:

Arteriosclerosis obliterans; Connexin 43; Methylation; Smooth muscle cell; microRNA

PMID:
26025955
DOI:
10.1093/cvr/cvv160
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center