Downregulation of long non‑coding RNA ANRIL promotes proliferation and migration in hypoxic human
pulmonary artery smooth muscle cells

Wang,Siqi; Zhang,Chen; Zhang,Xiaodan

doi:10.3892/mmr.2019.10887

Downregulation of long non‑coding RNA ANRIL promotes proliferation and migration in hypoxic human pulmonary artery smooth muscle cells

Authors:
- Siqi Wang
- Chen Zhang
- Xiaodan Zhang
View Affiliations

Affiliations: College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang 150076, P.R. China
Published online on: December 17, 2019 https://doi.org/10.3892/mmr.2019.10887
Pages: 589-596
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive syndrome. When PAH occurs, the circulatory resistance of the pulmonary vasculature will gradually increase, which may lead to right heart failure and death. Pathological features of PAH include abnormal proliferation of pulmonary vascular smooth muscle cells and pulmonary vascular remodeling. Hypoxia is the main cause of PAH, which directly induces the contraction and proliferation of pulmonary artery smooth muscle cells (PASMCs), and eventually leads to pulmonary vascular remodeling. Recent studies have shown that long non‑coding RNAs (lncRNAs) play key roles in numerous biological processes, including cell proliferation and the occurrence and development of cardiovascular diseases. Studies have also shown that lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) can promote the proliferation of vascular smooth muscle cells. Therefore, the hypothesis of the present study was that ANRIL may be expressed in PASMCs and play a regulatory role. In this study, the expression of ANRIL was analyzed by quantitative PCR. The effects of ANRIL on human pulmonary artery smooth muscle cells (HPASMCs) were assessed by MTT assay, flow cytometry, bromodeoxyuridine incorporation assay, Transwell assay, scratch‑wound assay, immunofluorescence assay and western blotting. These experiments revealed that the expression of ANRIL was significantly downregulated in HPASMCs induced by hypoxia. The downregulation of ANRIL affected the cell cycle, making more HPASMCs move from the G0/G1 phase to the G2/M+S phase and strengthening the cell proliferation. Moreover, downregulated ANRIL increased the migration of HPASMCs under hypoxia. This study identified ANRIL as a critical regulator in HPASMCs induced by hypoxia and demonstrated the potential of gene therapy and drug development for treating PAH.

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