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

Tan,Hong; Yao,Hua; Lie,Zhenbang; Chen,Guo; Lin,Shuguang; Zhang,Ying

doi:10.3892/mmr.2019.10251

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

Authors:
- Hong Tan
- Hua Yao
- Zhenbang Lie
- Guo Chen
- Shuguang Lin
- Ying Zhang
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Affiliations: Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, P.R. China
Published online on: May 16, 2019 https://doi.org/10.3892/mmr.2019.10251
Pages: 236-244
Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary arterial hypertension (PAH) is a fatal and currently incurable cardiopulmonary disease. Numerous microRNAs (miRNAs) 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 (HPAECs) when compared with the hypoxia‑induced group at 0 h. miR‑30a‑5p overexpression promoted HPAEC growth and inhibited apoptosis of HPAECs 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 HPAECs under hypoxia. In conclusion, the data indicated that miR‑30a‑5p promoted cell growth and inhibited apoptosis of HPAECs 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.

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