MicroRNA-30a-5p promotes proliferation and inhibits apoptosis of human pulmonary artery endothelial cells under hypoxia by targeting YKL-40

Abstract

Pulmonary arterial hypertension (PAH) is a fatal and currently incurable cardiopulmonary disease. Numerous microRNA s (miRNA s) serve important roles in the development of PAH. While the expression of miR- 30a-5p was downregulated in the lung tissue of rats in a pulmonary hypertension rat model, the expression pattern and function of miR- 30a-5p in human PAH remain unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR ) was used to examine miR- 30a-5p and chitinase-3-like protein 1 (YKL- 40) mRNA expression levels. The expression levels of YKL- 40 and apoptosis-associated proteins were measured by western blot analysis. Cell proliferation assays and flow cytometry analysis were performed to examine cell proliferation and apoptosis, respectively. The association between miR- 30a-5p and YKL- 40 was determined by a luciferase reporter assay, RT-qPCR and western blot analysis. The relative expression levels of miR- 30a-5p in plasma were increased in patients with PAH [median=13.23 (25th percentile=6.388, 75th percentile=21.91)] compared with normal controls [median=2.25 (25th percentile=1.4, 75th percentile=3.7). The expression of miR-30a-5p was significantly downregulated while the protein expression of YKL- 40 was significantly upregulated in hypoxia-induced human pulmonary artery endothelial cells (HPAEC s) when compared with the hypoxia-induced group at 0 h. miR- 30a-5p overexpression promoted HPAEC growth and inhibited apoptosis of HPAEC s under hypoxia. A miR- 30a-5p mimic decreased the luciferase activity of a luciferase reporter construct containing YKL- 40 3'-untranslated region and also decreased YKL- 40 protein expression. YKL- 40 overexpression partly alleviated the effects of miR- 30a-5p upregulation on proliferation and apoptosis of HPAEC s under hypoxia. In conclusion, the data indicated that miR- 30a-5p promoted cell growth and inhibited apoptosis of HPAEC s under hypoxia by targeting YKL- 40. Therefore, the miR- 30a-5p/YKL- 40 axis may provide a potential target for the development of novel PAH therapies.