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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
- 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.
- Subjects :
- Inflammation
Pulmonary and Respiratory Medicine
Pulmonary Arterial Hypertension
SOXB1 Transcription Factors
Myocytes, Smooth Muscle
Apoptosis
Pulmonary Artery
Critical Care and Intensive Care Medicine
MicroRNAs
Cell Movement
Humans
Familial Primary Pulmonary Hypertension
RNA, Long Noncoding
Hypoxia
Cardiology and Cardiovascular Medicine
Cell Proliferation
Subjects
Details
- ISSN :
- 01479563
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Heart & Lung
- Accession number :
- edsair.doi.dedup.....22dce522c2bfe938d159bf784dc7e101