Circ_0000029 Interacts with the miR-576-5p/KCNA1 Axis to Hamper the Development of Pediatric Asthma in an Asthma-Like in vitro Assessment.

Autor: Wang R; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Tan Y; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Bao X; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Xiong S; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Liang R; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Cai M; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China., Bian J; Department of Paediatrics, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China junmeibian@163.com.
Jazyk: angličtina
Zdroj: Annals of clinical and laboratory science [Ann Clin Lab Sci] 2023 Mar; Vol. 53 (2), pp. 200-211.
Abstrakt: Objective: Numerous circular RNAs (circRNAs) have been verified to execute crucial roles in "asthma-like" progression of the airway smooth muscle cells (ASMCs). The present study aimed to scrutinize the function and mechanism of circ_0000029 in pediatric asthma etiology in vitro .
Methods: A cell model of asthma was developed using ASMCs induced by platelet-derived growth factor BB (PDGF-BB). Western blotting and qRT-PCR were performed to determine the expression levels of circ_0000029, miR-576-5p, and KCNA1 in PDGF-BB-treated ASMCs. Dual-luciferase reporter, RNA-binding protein immunoprecipitation, and RNA pull-down experiments were conducted to validate targeting relationships. CCK-8 and Transwell assays were performed to evaluate the proliferative and migratory potential of ASMCs. The rate of apoptosis was analyzed using flow cytometry.
Results: Pronounced circ_0000029 and KCNA1 downregulation and high levels of miR-576-5p were observed in PDGF-BB-treated ASMCs. Circ_0000029 targets miR-576-5p to regulate KCNA1 expression. The loss of KCNA1 and upregulation of miR-576-5p dramatically impeded apoptosis but promoted ASMC migration and proliferation. Ectopic expression of circ_0000029 manifested the opposite outcome among ASMCs. Furthermore, KCNA1 deficiency and miR-576-5p upregulation counteracted the effects of circ_0000029 overexpression on ASMCs.
Conclusions: Circ_0000029 represses the abnormal migration and growth of ASMCs by mediating miR-576-5p and KCNA1 expression levels. This suggests that the regulatory axis circ_0000029/miR-576-5p/KCNA1 is a potential target for pediatric asthma treatment.
(© 2023 by the Association of Clinical Scientists, Inc.)
Databáze: MEDLINE