LincRNA-Cox2 promotes pulmonary arterial hypertension by regulating the let-7a-mediated STAT3 signaling pathway
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LincRNA‑Cox2 promotes pulmonary arterial hypertension by regulating the let‑7a‑mediated STAT3 signaling pathway Gesheng Cheng1 · Lu He1 · Yushun Zhang1 Received: 5 March 2020 / Accepted: 7 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract It is well supported by the literature that the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are critical for the development of pulmonary arterial hypertension (PAH). Long intergenic noncoding RNA COX2 (lincRNACOX2) is a regulator of inflammation and might be conducive to the progression of atherosclerosis, while its role in PAH is still unclear. This study was performed to explore the role and mechanism of lincRNA-COX2 in PASMCs proliferation and migration in an anaerobic environment. PASMCs were treated by hypoxia to construct PAH cell models. RT-PCR and western blot were recruited to evaluate the expression levels of lincRNA-COX2, miR-let-7a and STAT3. Their roles in proliferation and cell and migration of PASMCs were determined by the CCK-8 assay, wound-healing assay, and flow cytometry. In peripheral blood samples from PAH patients and hypoxic PASMCs, lincRNA-COX2 expression was enhanced. Silencing lincRNA-COX2 inhibited hypoxia-induced PASMCs proliferation by influencing the G2/M phase of the cell cycle. Meanwhile, lincRNA-COX2 regulated STAT3 through miR-let-7a and its effects on hypoxic PASMCs worked through miR-let-7a/ STAT3 axis. To conclude, silencing lincRNA-COX2 attenuated the development of hypoxic PASMCs. LincRNA-COX2/ miR-let-7a/STAT3 axis might be considered as a novel target to treat PAH. Keywords Linc-Cox2 · Let-7a · STAT3 signaling pathway · Pulmonary arterial hypertension · Proliferation · Migration
Introduction Pulmonary arterial hypertension (PAH) refers to the mPAP (mean pulmonary artery pressure) greater than 25 mmHg in resting conditions [1, 2]. Patients often have high pulmonary artery pressure without obvious symptoms, resulting in right heart failure and even death. Pulmonary vascular remodeling and increased pulmonary artery resistance are the critical pathogenesis of PAH [3]. Pulmonary artery remodeling is mainly caused by abnormal growth, excessive proliferation and decreased anti-apoptotic ability of smooth muscle cells [4]. Therefore, the inhibition of pulmonary arteriole smooth muscle cells (PASMCs) proliferation or the induction of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03877-6) contains supplementary material, which is available to authorized users. * Yushun Zhang [email protected] 1
Department of Structural Heart Disease, First Affiliated Hospital of Xi’an Jiaotong University, 277# West Yanta Road, Xi’an 710061, Shaanxi, China
smooth muscle cell apoptosis is an effective therapeutic strategy for PAH. Long noncoding RNAs (lncRNAs), which are more than 200 nt in length, form a newly discovered class of RNA molecules with strong biological regulatory capacity. Quinodoz et al. identified thous
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