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Dysregulation of microRNA-214 and PTEN contributes to the pathogenesis of hypoxic pulmonary hypertension

Authors Liu H, Yin T, Yan W, Si R, Wang B, Chen M, Li F, Wang Q, Tao L

Received 20 January 2016

Accepted for publication 25 February 2016

Published 19 June 2017 Volume 2017:12 Pages 1781—1791

DOI https://doi.org/10.2147/COPD.S104627

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 4

Editor who approved publication: Dr Richard Russell

HaiTao Liu, Tao Yin, Wenjun Yan, Rui Si, Bo Wang, Mai Chen, Fei Li, Qiong Wang, Ling Tao

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China

Abstract: Hypoxia-induced pulmonary hypertension, which is characterized by vascular remodeling of blood vessels, is an important complication in COPD. In this study, we found that the expression of miR-214 was differentially expressed by screening 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs). Additionally, using luciferase assay in PASMCs, we found that phosphatase-and-tensin homolog (PTEN) was a target of miR-214. Furthermore, the expression of PTEN was found to be substantially downregulated in PASMCs from COPD patients with pulmonary hypertension (PH) compared with normal controls by using real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. In addition, we transfected PASMCs with miR-214 mimics, using real-time PCR and Western blotting, to confirm the miRNA/mRNA relationship. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing apoptosis of the cells, which was mediated by the downregulation of PTEN. Exposure to hypoxia significantly increased the expression of miR-214 and decreased the expression of PTEN in PASMCs, and its proliferation was significantly promoted. Such effects could be significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated the expression of PTEN. In conclusion, hypoxia-induced upregulation of miR-214 was found to promote PH development by targeting PTEN in PASMCs, and miR-214 could be a promising diagnostic tool and novel therapeutic target in the management of hypoxia-induced PH in COPD.

Keywords: hypoxia, pulmonary hypertension, miR-214, PTEN

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