circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promotes hypoxic pulmonary arterial smooth muscle cell proliferation in COPD

Autor: Wang Changguo, Liu Yingying, Zhang Weiyun, Huang Jian’an, Jiang Junhong, Wang Ran, Zeng Daxiong
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Acta Biochimica et Biophysica Sinica, Vol 55, Pp 438-448 (2022)
Druh dokumentu: article
ISSN: 1672-9145
DOI: 10.3724/abbs.2022178
Popis: Hypoxia plays a crucial role in pulmonary vascular remodelling at the early stage of chronic obstructive pulmonary disease (COPD). Circle RNA (circRNA) has been identified to play a critical role in multiple diseases. However, the role of circRNAs in pulmonary vascular remodelling in COPD remains unclear. In this study, we aim to investigate the role of circRNAs in pulmonary arterial smooth muscle cell proliferation and pulmonary vascular remodelling in COPD. COPD patients show lower partial pressure of arterial oxygen and pulmonary arterial remodeling as compared with controls. circRNA microarray and real-time PCR analyses show significantly higher level of circ-BPTF and lower miR-486-5p level in the pulmonary arteries of COPD patients as compared with controls. Hypoxia suppresses miR-486-5p expression but promotes expressions of circ-BPTF and cell migration inducing protein (CEMIP) in human pulmonary arterial smooth muscle cells (PASMCs) in vitro. Loss- and gain-of-function experiments show that circ-BPTF promotes PASMC proliferation in vitro. Moreover, luciferase reporter assay results indicate that circ-BPTF regulates PASMC proliferation by acting as an miR-486-5p sponge. CEMIP is identified as a candidate target gene of miR-486-5p by luciferase reporter assay. Overall, our study shows that circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promote hypoxic PASMC proliferation in pulmonary vascular remodelling in COPD.
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