Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis

The proliferation and migration of pulmonary artery endothelial cells are the pathological basis of pulmonary vascular remodeling with pulmonary hypertension. Recent studies have shown that circular RNA (circRNA) regulates biological processes in various vascular diseases, including pulmonary arteri...

Full description

Bibliographic Details
Main Authors: Liuqing Hong, Xiaoying Ma, Jiyuan Liu, Yinzhu Luo, Jincai Lin, Ying Shen, Liyan Zhang
Format: Article
Language:English
Published: Wiley 2021-03-01
Series:Pulmonary Circulation
Online Access:https://doi.org/10.1177/20458940211000234
_version_ 1811230763858788352
author Liuqing Hong
Xiaoying Ma
Jiyuan Liu
Yinzhu Luo
Jincai Lin
Ying Shen
Liyan Zhang
author_facet Liuqing Hong
Xiaoying Ma
Jiyuan Liu
Yinzhu Luo
Jincai Lin
Ying Shen
Liyan Zhang
author_sort Liuqing Hong
collection DOAJ
description The proliferation and migration of pulmonary artery endothelial cells are the pathological basis of pulmonary vascular remodeling with pulmonary hypertension. Recent studies have shown that circular RNA (circRNA) regulates biological processes in various vascular diseases, including pulmonary arterial hypertension. It has been reported that circRNA regulates the vascular endothelial cells’ function. Therefore, circRNA may have crucial roles in human pulmonary artery endothelial cells (hPAECs) proliferation, migration, and tube formation in pulmonary arterial hypertension. In this study, we aimed to discover the role and mechanism of circular RNA HIPK3 (circHIPK3) in the proliferation and migration of pulmonary hypertension hPAECs. First, we used platelet-derived growth factor—stimulated hPAECs as a cellular model of pulmonary arterial hypertension. The results showed that platelet-derived growth factor promoted hPAECs proliferation, migration, and tube formation. Notably, platelet-derived growth factor upregulated the expression of circHIPK3 in hPAECs and regulated their proliferation, migration, and angiogenesis. Mechanistically, we confirmed miR-328-3p was copiously pulled down by circHIPK3 in hPAECs. Luciferase reporter and RNA immunoprecipitation assays further indicated the cytoplasmic interactions between circHIPK3 and miR-328-3p. Subsequently, we found that circHIPK3 might increase the expression of STAT3 by sponging miR-328-3p. Collectively, our results demonstrated that the circHIPK3-miR-328-3p-STAT3 axis contributed to the pathogenesis of pulmonary arterial hypertension by stimulating hPAECs proliferation, migration, and angiogenesis. The circHIPK3 has an accelerated role in pulmonary arterial hypertension development, implicating the potential values of circHIPK3 in pulmonary arterial hypertension therapy.
first_indexed 2024-04-12T10:33:25Z
format Article
id doaj.art-310f917365204e26b678cba985cd3548
institution Directory Open Access Journal
issn 2045-8940
language English
last_indexed 2024-04-12T10:33:25Z
publishDate 2021-03-01
publisher Wiley
record_format Article
series Pulmonary Circulation
spelling doaj.art-310f917365204e26b678cba985cd35482022-12-22T03:36:47ZengWileyPulmonary Circulation2045-89402021-03-011110.1177/20458940211000234Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axisLiuqing HongXiaoying MaJiyuan LiuYinzhu LuoJincai LinYing ShenLiyan ZhangThe proliferation and migration of pulmonary artery endothelial cells are the pathological basis of pulmonary vascular remodeling with pulmonary hypertension. Recent studies have shown that circular RNA (circRNA) regulates biological processes in various vascular diseases, including pulmonary arterial hypertension. It has been reported that circRNA regulates the vascular endothelial cells’ function. Therefore, circRNA may have crucial roles in human pulmonary artery endothelial cells (hPAECs) proliferation, migration, and tube formation in pulmonary arterial hypertension. In this study, we aimed to discover the role and mechanism of circular RNA HIPK3 (circHIPK3) in the proliferation and migration of pulmonary hypertension hPAECs. First, we used platelet-derived growth factor—stimulated hPAECs as a cellular model of pulmonary arterial hypertension. The results showed that platelet-derived growth factor promoted hPAECs proliferation, migration, and tube formation. Notably, platelet-derived growth factor upregulated the expression of circHIPK3 in hPAECs and regulated their proliferation, migration, and angiogenesis. Mechanistically, we confirmed miR-328-3p was copiously pulled down by circHIPK3 in hPAECs. Luciferase reporter and RNA immunoprecipitation assays further indicated the cytoplasmic interactions between circHIPK3 and miR-328-3p. Subsequently, we found that circHIPK3 might increase the expression of STAT3 by sponging miR-328-3p. Collectively, our results demonstrated that the circHIPK3-miR-328-3p-STAT3 axis contributed to the pathogenesis of pulmonary arterial hypertension by stimulating hPAECs proliferation, migration, and angiogenesis. The circHIPK3 has an accelerated role in pulmonary arterial hypertension development, implicating the potential values of circHIPK3 in pulmonary arterial hypertension therapy.https://doi.org/10.1177/20458940211000234
spellingShingle Liuqing Hong
Xiaoying Ma
Jiyuan Liu
Yinzhu Luo
Jincai Lin
Ying Shen
Liyan Zhang
Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
Pulmonary Circulation
title Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
title_full Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
title_fullStr Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
title_full_unstemmed Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
title_short Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis
title_sort circular rna hipk3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microrna 328 3p stat3 axis
url https://doi.org/10.1177/20458940211000234
work_keys_str_mv AT liuqinghong circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT xiaoyingma circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT jiyuanliu circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT yinzhuluo circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT jincailin circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT yingshen circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis
AT liyanzhang circularrnahipk3regulateshumanpulmonaryarteryendothelialcellsfunctionandvesselgrowthbyregulatingmicrorna3283pstat3axis