The Mechanism of MicroRNA-486-5p the Function of Hypoxia-Induced Pulmonary Artery Smooth Muscle Cell: A Laboratory Case-Control Study

作者：Li, Hai-rong; Chen, Guan-liang; Fang, Xiao-li; Cai, Xing-jiu; Xu, Rong-li; Li, Dong-dong; Zhang, Zhi-wei^*

来源：JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS, 2022, 36(6): 2037-2046.

DOI：10.23812/j.biol.regul.homeost.agents.20223606.211

• human pulmonary artery smooth muscle cells (hPASMCs)
• pulmonary arterial hypertension (PAH)
• hypoxia
• microRNA-486-5p
• phosphatidylinositol4,5-bisphosphate 3-kinase/protein kinase B (PI3K/Akt)
• phosphatase and tensin homolog deleted on chro-10 (PTEN)

Background: miRNAs can control the hypernomic proliferation of pulmonary artery smooth muscles (PASMCs), which is im-plicated in the pulmonary arterial hypertension (PAH) development. However, the mechanism of miRNAs is unknown, so this study was expected to explore it. @@@ Methods: Up-regulated miRNAs were analyzed in data sets GSE21284 and GSE67597 associated with PAH, and sera from PAH patients and healthy volunteers were collected and human PASMCs (hPASMCs) were cultured under hypoxic and normoxic conditions, to check for up-regulated miRNAs expressions via quantitative real-time polymerase chain reaction (qRT-PCR). Fol-lowing screening miR-486-5p out, the target relationship of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and miR-486-5p was predicted and validated, using bioinformatics website and dual-luciferase reporter assay. Next, miR-486-5p or PTEN expression was interfered, then cell migration ability, proliferation level, and apoptosis level were observed, using CCK-8 (Cell Counting Kit-8), flow cytometry and scratch assays; Besides, the PI3K/Akt (phosphatidylinositol4,5-bisphosphate 3-kinase/protein kinase B) signaling pathway-related protein expression of cells was checked, using Western blot. @@@ Results: PTEN expression was significantly down-regulated while miR-486-5p was greatly mounted in hypoxia-cultured hPASMCs and in the serum of PAH patients. Knocked down of miR-486-5p caused a significant reduction in PI3K/Akt axis activity, inhibition of hPASMC migration and proliferation under normoxic and hypoxic circumstances, and increase in apopto-sis. Importantly, a target relationship was detected between PTEN and miR-486-5p, and the function of this RNA was significantly restored by knocking what down. @@@ Conclusions: miR-486-5p can activate PI3K/Akt signaling to regulate the function of hypoxia-induced hPASMCs, through tar-geting PTEN.

• 单位
  广东省人民医院; 海南医学院; 广东省心血管病研究所; 南方医科大学