LincRNA-Cox2 promotes pulmonary arterial hypertension by regulating the let-7a-mediated STAT3 signaling pathway.
2020
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 (lincRNA-COX2) 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.
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