NEAT1 silencing alleviates pulmonary arterial smooth muscle cell migration and proliferation under hypoxia through regulation of miR‑34a‑5p/KLF4 <em>in vitro</em>

Dou,Xiuli; Ma,Yuxiao; Qin,Yijie; Dong,Qinglin; Zhang,Shouwei; Tian,Rui; Pan,Mingyu

doi:10.3892/mmr.2021.12389

NEAT1 silencing alleviates pulmonary arterial smooth muscle cell migration and proliferation under hypoxia through regulation of miR‑34a‑5p/KLF4 in vitro

Authors:
- Xiuli Dou
- Yuxiao Ma
- Yijie Qin
- Qinglin Dong
- Shouwei Zhang
- Rui Tian
- Mingyu Pan
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Affiliations: Department of Emergency, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Emergency, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Medical, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of Cardiology, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China
Published online on: August 31, 2021 https://doi.org/10.3892/mmr.2021.12389
Article Number: 749

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Abstract

Pulmonary arterial hypertension (PAH) is a severe vascular disease that adversely affects patient health and can be life threatening. The present study aimed to investigate the detailed role of nuclear paraspeckle assembly transcript 1 (NEAT1) in PAH. Using RT‑qPCR, the expression levels of NEAT1, microRNA (miR)‑34a‑5p, and Krüppel‑like factor 4 (KLF4) were detected in both hypoxia‑treated pulmonary arterial smooth muscle cells (PASMCs) and serum from PAH patients. Then, the interactions among miR‑34a‑5p, NEAT1, and KLF4 were evaluated by dual‑luciferase reporter assay. The detailed role of the NEAT1/miR‑34a‑5p/KLF4 axis in PAH pathogenesis was further explored using MTT, Transwell, and western blot assays. The results revealed that NEAT1 targeted miR‑34a‑5p and miR‑34a‑5p targeted KLF4. In hypoxia‑treated PASMCs and serum from PAH patients, high NEAT1 and KLF4 expression levels and low miR‑34a‑5p expression were observed. The proliferation and migration of hypoxia‑treated PASMCs were reduced by transfection with sh‑NEAT1 or miR‑34a‑5p mimics. The suppressive effects of NEAT1 knockdown on the proliferation and migration of hypoxia‑treated PASMCs were reversed by knock down of miR‑34a‑5p expression and increased KLF4 expression. NEAT1 was not only highly expressed in the serum of PAH patients but its silencing also alleviated PAH by regulating miR‑34a‑5p/KLF4 in vitro. The present study highlighted a potential new therapeutic target and diagnostic biomarker for PAH.

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