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Clinical value of lncRNA SOX2-OT in pulmonary arterial hypertension and its role in pulmonary artery smooth muscle cell proliferation, migration, apoptosis, and inflammatory

Authors :
Yunfei, Jiang
Bingchang, Hei
Wenbo, Hao
Shudong, Lin
Yuanyuan, Wang
Xuzhi, Liu
Xianguo, Meng
Zhanjiang, Guan
Source :
Heart & Lung. 55:16-23
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Non-coding RNA is confirmed to be involved in pulmonary arterial hypertension (PAH).This study investigated the clinical value and potential mechanisms of the long noncoding RNA (lncRNA) SRY-box transcription factor 2 overlapping transcript (SOX2-OT) in PAH.SOX2-OT levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in serum of 82 patients with PAH and 76 healthy controls. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of SOX2-OT. Human pulmonary arterial smooth muscle cells (hPASMCs) were treated by hypoxia to construct PAH cell models. Proliferation, migration, apoptosis, and inflammatory cytokines levels of hPASMCs were examined by CCK-8, Transwell, flow cytometry, and ELISA assay. Dual-luciferase reporter gene assays were performed to verify the target relationships between miR-455-3p and SOX2-OT, as well as small ubiquitin-related modifier 1 (SUMO1).Serum SOX2-OT was highly expressed in patients with PAH (P0.05). And elevated SOX2-OT levels significantly differentiated PAH patients from healthy controls, confirming high diagnostic feasibility. What's more, SOX2-OT was increased in hypoxia-induced hPASMCs in a time-dependent manner. Silencing SOX2-OT could reverse hypoxia-induced proliferation, migration, anti-apoptosis, and inflammation of hPASMCs (P0.05). However, rescue experiments showed that this reversal effect of silencing SOX2-OT was attenuated by suppressed miR-455-3p, which was presumably achieved by SUMO1 (P0.05).Elevated SOX2-OT is a feasible diagnostic marker for PAH, and its silencing may attenuated hypoxia-induced hPASMCs proliferation, migration, anti-apoptosis, and inflammation by modulating the miR-455-3p/SUMO1 axis, preventing vascular remodeling and PAH progression. Our research provided new insights for PAH treatment.

Details

ISSN :
01479563
Volume :
55
Database :
OpenAIRE
Journal :
Heart & Lung
Accession number :
edsair.doi.dedup.....22dce522c2bfe938d159bf784dc7e101