Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression

Hypoxia induces the abnormal proliferation of vascular smooth muscle cells (VSMCs), resulting in the pathogenesis of various vascular diseases. RNA-binding proteins (RBPs) are involved in a wide range of biological processes, including cell proliferation and responses to hypoxia. In this study, we o...

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Main Authors: Jihui Lee, Hara Kang
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/5/817
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author Jihui Lee
Hara Kang
author_facet Jihui Lee
Hara Kang
author_sort Jihui Lee
collection DOAJ
description Hypoxia induces the abnormal proliferation of vascular smooth muscle cells (VSMCs), resulting in the pathogenesis of various vascular diseases. RNA-binding proteins (RBPs) are involved in a wide range of biological processes, including cell proliferation and responses to hypoxia. In this study, we observed that the RBP nucleolin (NCL) was downregulated by histone deacetylation in response to hypoxia. We evaluated its regulatory effects on miRNA expression under hypoxic conditions in pulmonary artery smooth muscle cells (PASMCs). miRNAs associated with NCL were assessed using RNA immunoprecipitation in PASMCs and small RNA sequencing. The expression of a set of miRNAs was increased by NCL but reduced by hypoxia-induced downregulation of NCL. The downregulation of miR-24-3p and miR-409-3p promoted PASMC proliferation under hypoxic conditions. These results clearly demonstrate the significance of NCL–miRNA interactions in the regulation of hypoxia-induced PASMC proliferation and provide insight into the therapeutic value of RBPs for vascular diseases.
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spelling doaj.art-8ee98b6bd12d48279b4c46e3f0ba45662023-11-17T07:28:33ZengMDPI AGCells2073-44092023-03-0112581710.3390/cells12050817Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA ExpressionJihui Lee0Hara Kang1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of KoreaHypoxia induces the abnormal proliferation of vascular smooth muscle cells (VSMCs), resulting in the pathogenesis of various vascular diseases. RNA-binding proteins (RBPs) are involved in a wide range of biological processes, including cell proliferation and responses to hypoxia. In this study, we observed that the RBP nucleolin (NCL) was downregulated by histone deacetylation in response to hypoxia. We evaluated its regulatory effects on miRNA expression under hypoxic conditions in pulmonary artery smooth muscle cells (PASMCs). miRNAs associated with NCL were assessed using RNA immunoprecipitation in PASMCs and small RNA sequencing. The expression of a set of miRNAs was increased by NCL but reduced by hypoxia-induced downregulation of NCL. The downregulation of miR-24-3p and miR-409-3p promoted PASMC proliferation under hypoxic conditions. These results clearly demonstrate the significance of NCL–miRNA interactions in the regulation of hypoxia-induced PASMC proliferation and provide insight into the therapeutic value of RBPs for vascular diseases.https://www.mdpi.com/2073-4409/12/5/817pulmonary artery smooth muscle cellsnucleolinhypoxiamicroRNA
spellingShingle Jihui Lee
Hara Kang
Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
Cells
pulmonary artery smooth muscle cells
nucleolin
hypoxia
microRNA
title Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
title_full Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
title_fullStr Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
title_full_unstemmed Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
title_short Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression
title_sort nucleolin regulates pulmonary artery smooth muscle cell proliferation under hypoxia by modulating mirna expression
topic pulmonary artery smooth muscle cells
nucleolin
hypoxia
microRNA
url https://www.mdpi.com/2073-4409/12/5/817
work_keys_str_mv AT jihuilee nucleolinregulatespulmonaryarterysmoothmusclecellproliferationunderhypoxiabymodulatingmirnaexpression
AT harakang nucleolinregulatespulmonaryarterysmoothmusclecellproliferationunderhypoxiabymodulatingmirnaexpression