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LincRNA-Cox2 promotes pulmonary arterial hypertension by regulating the let-7a-mediated STAT3 signaling pathway.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2020-08-14 , DOI: 10.1007/s11010-020-03877-6
Gesheng Cheng 1 , Lu He 1 , Yushun Zhang 1
Affiliation  

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.



中文翻译:

LincRNA-Cox2通过调节let-7a介导的STAT3信号通路来促进肺动脉高压。

文献充分支持肺动脉平滑肌细胞(PASMC)的增殖和迁移对于肺动脉高压(PAH)的发展至关重要。较长的基因间非编码RNA COX2(lincRNA-COX2)是炎症的调节剂,可能有助于动脉粥样硬化的发展,尽管其在PAH中的作用仍不清楚。进行这项研究以探讨lincRNA-COX2在厌氧环境下PASMCs增殖和迁移中的作用和机制。通过缺氧处理PASMC,以构建PAH细胞模型。募集了RT-PCR和Western blot来评估lincRNA-COX2,miR-let-7a和STAT3的表达水平。通过CCK-8测定,伤口愈合测定和流式细胞术确定了它们在PASMCs增殖,细胞和迁移中的作用。在PAH患者和低氧PASMCs的外周血样本中,lincRNA-COX2表达增强。沉默lincRNA-COX2可以通过影响细胞周期的G2 / M期来抑制缺氧诱导的PASMCs增殖。同时,lincRNA-COX2通过miR-let-7a调控STAT3,并通过miR-let-7a / STAT3轴对缺氧的PASMC产生影响。总而言之,沉默lincRNA-COX2会减弱低氧PASMC的发育。LincRNA-COX2 / miR-let-7a / STAT3轴可能被认为是治疗PAH的新靶标。总而言之,沉默lincRNA-COX2会减弱低氧PASMC的发育。LincRNA-COX2 / miR-let-7a / STAT3轴可能被视为治疗PAH的新靶标。总而言之,沉默lincRNA-COX2会减弱低氧PASMC的发育。LincRNA-COX2 / miR-let-7a / STAT3轴可能被视为治疗PAH的新靶标。

更新日期:2020-08-14
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