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CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension

Background We recently demonstrated that circGSAP was diminished in lung tissues from patients with pulmonary arterial hypertension and in hypoxia-induced pulmonary microvascular endothelial cells (PMECs). However, the underlying role of circGSAP in PMECs remains unknown. The study aimed to investig...

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Autores principales: Sun, Yuanyuan, Wu, Wenhui, Zhao, Qinhua, Jiang, Rong, Li, Jinling, Wang, Lan, Xia, Shijin, Liu, Mingjie, Gong, Sugang, Liu, Jinming, Yuan, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428790/
https://www.ncbi.nlm.nih.gov/pubmed/36060794
http://dx.doi.org/10.3389/fcell.2022.967708
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author Sun, Yuanyuan
Wu, Wenhui
Zhao, Qinhua
Jiang, Rong
Li, Jinling
Wang, Lan
Xia, Shijin
Liu, Mingjie
Gong, Sugang
Liu, Jinming
Yuan, Ping
author_facet Sun, Yuanyuan
Wu, Wenhui
Zhao, Qinhua
Jiang, Rong
Li, Jinling
Wang, Lan
Xia, Shijin
Liu, Mingjie
Gong, Sugang
Liu, Jinming
Yuan, Ping
author_sort Sun, Yuanyuan
collection PubMed
description Background We recently demonstrated that circGSAP was diminished in lung tissues from patients with pulmonary arterial hypertension and in hypoxia-induced pulmonary microvascular endothelial cells (PMECs). However, the underlying role of circGSAP in PMECs remains unknown. The study aimed to investigate the contribution of circGSAP to proliferation, apoptosis and cell cycle of PMECs in hypoxic environment and explore the mechanism. Methods The expression of circGSAP was quantified by real-time PCR or immunofluorescence in human lung tissue and PMECs. CircGSAP plasmid, circGSAP small interfering RNA (siRNA), miRNA inhibitor and target gene siRNA were synthesized to verify the role of circGSAP on regulating the proliferation, apoptosis, and cell cycle of PMECs. Results CircGSAP levels were decreased in lungs and plasma of patients with pulmonary hypertension second to chronic obstructive pulmonary disease (COPD-PH) and were associated with poor outcomes of COPD-PH patients. Upregulation of circGSAP inhibited proliferation, apoptosis resistance and G1/S transition of PMECs. Dual luciferase reporter assays showed that circGSAP acted as a competitive endogenous RNA regulating miR-942-5p, and identified SMAD4 as a target gene of miR-942-5p, Then, we verified the functions of miR-942-5p and SMAD4 in PMECs. In addition, the effect of circGSAP siRNA on PMECs was mitigated by transfection of miR-942-5p inhibitor, and the effect of miR-942-5p inhibitor on PMECs was inhibited by SMAD4 siRNA. Conclusion Our findings demonstrated that diminished circGSAP accelerated cell cycle to facilitate cell proliferation and apoptosis resistance through competitively binding miR-942-5p to modulate SMAD4 expressions in hypoxia-induced PMECs, indicating potential therapeutic strategies for PH.
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spelling pubmed-94287902022-09-01 CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension Sun, Yuanyuan Wu, Wenhui Zhao, Qinhua Jiang, Rong Li, Jinling Wang, Lan Xia, Shijin Liu, Mingjie Gong, Sugang Liu, Jinming Yuan, Ping Front Cell Dev Biol Cell and Developmental Biology Background We recently demonstrated that circGSAP was diminished in lung tissues from patients with pulmonary arterial hypertension and in hypoxia-induced pulmonary microvascular endothelial cells (PMECs). However, the underlying role of circGSAP in PMECs remains unknown. The study aimed to investigate the contribution of circGSAP to proliferation, apoptosis and cell cycle of PMECs in hypoxic environment and explore the mechanism. Methods The expression of circGSAP was quantified by real-time PCR or immunofluorescence in human lung tissue and PMECs. CircGSAP plasmid, circGSAP small interfering RNA (siRNA), miRNA inhibitor and target gene siRNA were synthesized to verify the role of circGSAP on regulating the proliferation, apoptosis, and cell cycle of PMECs. Results CircGSAP levels were decreased in lungs and plasma of patients with pulmonary hypertension second to chronic obstructive pulmonary disease (COPD-PH) and were associated with poor outcomes of COPD-PH patients. Upregulation of circGSAP inhibited proliferation, apoptosis resistance and G1/S transition of PMECs. Dual luciferase reporter assays showed that circGSAP acted as a competitive endogenous RNA regulating miR-942-5p, and identified SMAD4 as a target gene of miR-942-5p, Then, we verified the functions of miR-942-5p and SMAD4 in PMECs. In addition, the effect of circGSAP siRNA on PMECs was mitigated by transfection of miR-942-5p inhibitor, and the effect of miR-942-5p inhibitor on PMECs was inhibited by SMAD4 siRNA. Conclusion Our findings demonstrated that diminished circGSAP accelerated cell cycle to facilitate cell proliferation and apoptosis resistance through competitively binding miR-942-5p to modulate SMAD4 expressions in hypoxia-induced PMECs, indicating potential therapeutic strategies for PH. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9428790/ /pubmed/36060794 http://dx.doi.org/10.3389/fcell.2022.967708 Text en Copyright © 2022 Sun, Wu, Zhao, Jiang, Li, Wang, Xia, Liu, Gong, Liu and Yuan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sun, Yuanyuan
Wu, Wenhui
Zhao, Qinhua
Jiang, Rong
Li, Jinling
Wang, Lan
Xia, Shijin
Liu, Mingjie
Gong, Sugang
Liu, Jinming
Yuan, Ping
CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title_full CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title_fullStr CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title_full_unstemmed CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title_short CircGSAP regulates the cell cycle of pulmonary microvascular endothelial cells via the miR-942-5p sponge in pulmonary hypertension
title_sort circgsap regulates the cell cycle of pulmonary microvascular endothelial cells via the mir-942-5p sponge in pulmonary hypertension
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428790/
https://www.ncbi.nlm.nih.gov/pubmed/36060794
http://dx.doi.org/10.3389/fcell.2022.967708
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