Department of Respiratory medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou 450014, China.
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou 450014, China.
Exp Cell Res. 2018 Feb 15;363(2):255-261. doi: 10.1016/j.yexcr.2018.01.015. Epub 2018 Jan 13.
MicroRNAs play a crucial role in the progression of pulmonary arterial hypertension (PAH). The aim of this study was to investigate the effect of miR-361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth muscle cells (PASMCs) that under the treatment of hypoxia and explore the underlying mechanisms. The results proved that hypoxia noticeably up-regulated the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated cells, while TNF-α and IL-6 stimulation had no obvious effects on miR-361-5p level. Hypoxia induced miR-361-5p elevation in a HIF-1α-dependent manner. Inhibition of miR-361-5p dramatically inhibited hypoxia-induced cell proliferation and migration. miR-361-5p inhibition also rescued hypoxia exposure caused suppression of PASMCs apoptosis. In addition, the results showed that ABCA1 was a direct target of miR-361-5p and was down-regulated in hypoxia-induced PASMCs. Hypoxia and TNF-α or IL-6 stimulation significantly inhibited ABCA1 expression. In addition, overexpression of ABCA1 enhanced the effect of miR-361-5p on hPASMCs. Furthermore, the inhibition of miR-361-5p significantly down-regulated the expression level of p-JAK2 and p-STAT3. In conclusion, it may suggest that the suppression of miR-361-5p suppressed PASMC survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.
微小 RNA 在肺动脉高压（PAH）的进展中发挥着关键作用。本研究旨在探讨 miR-361-5p 在缺氧处理下对肺动脉平滑肌细胞（PASMC）增殖、迁移和凋亡的影响，并探讨其潜在机制。结果表明，与常氧处理的细胞相比，缺氧显著上调了 PASMC 中 miR-361-5p 的表达，而 TNF-α和 IL-6 刺激对 miR-361-5p 水平没有明显影响。缺氧以 HIF-1α依赖性方式诱导 miR-361-5p 的升高。抑制 miR-361-5p 可显著抑制缺氧诱导的细胞增殖和迁移。miR-361-5p 抑制还挽救了缺氧暴露引起的 PASMC 凋亡抑制。此外，结果表明 ABCA1 是 miR-361-5p 的直接靶标，并在缺氧诱导的 PASMCs 中下调。缺氧和 TNF-α或 IL-6 刺激显著抑制 ABCA1 的表达。此外，ABCA1 的过表达增强了 miR-361-5p 对 hPASMCs 的作用。此外，抑制 miR-361-5p 可显著下调 p-JAK2 和 p-STAT3 的表达水平。综上所述，抑制 miR-361-5p 通过靶向 ABCA1 并抑制 JAK2/STAT3 通路抑制 PASMC 存活和迁移。
