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

Jihui Lee; Hara Kang

doi:10.3390/cells12050817

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

Cells. 2023 Mar 6;12(5):817. doi: 10.3390/cells12050817.

Authors

Jihui Lee¹, Hara Kang^{1

2}

Affiliations

¹ Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
² Institute for New Drug Development, Incheon National University, Incheon 22012, Republic of Korea.

Abstract

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.

Keywords: hypoxia; microRNA; nucleolin; pulmonary artery smooth muscle cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Hypoxia / genetics
Cell Proliferation / physiology
Humans
Hypoxia / metabolism
MicroRNAs* / genetics
Myocytes, Smooth Muscle / metabolism
Nucleolin
Pulmonary Artery / metabolism
RNA-Binding Proteins / metabolism
Vascular Diseases* / metabolism

Substances

MicroRNAs
RNA-Binding Proteins

Grants and funding

This work was supported by the Incheon National University Research Grant in 2020 and the Basic Science Research Program through the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (2019R1A2C1004053) to H.K.