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环状RNA circabcc4通过螯合miR-663a促进PLA2G6表达从而推动支气管肺发育不良进展

Promotion of Bronchopulmonary Dysplasia Progression Using Circular RNA circabcc4 via Facilitating PLA2G6 Expression by Sequestering miR-663a.

作者信息

Chen Yu-Fei, Feng Dan-Dan, Wu Sheng-Hua, Lu Hong-Yan, Banu Pasha Asfia, Permall Dhivya Lakshmi, Chen Jia-He, Sun Zhong-Yi, Li Bing-Jie, Zhou Huan, Yang Yang, Zhang Xiao-Jie, Chen Xiao-Qing

机构信息

Department of Pediatrics, The First Affliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Pediatrics, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.

出版信息

Front Cell Dev Biol. 2020 Oct 27;8:585541. doi: 10.3389/fcell.2020.585541. eCollection 2020.

DOI:10.3389/fcell.2020.585541
PMID:33195232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7654334/
Abstract

Circular RNA (circRNA) has been increasingly proven as a new type of promising therapeutic RNA molecule in a variety of human diseases. However, the role of circRNA in bronchopulmonary dysplasia (BPD) has not yet been elucidated. Here, a new circRNA circABCC4 was identified from the Agilent circRNA chip as a differentially expressed circRNA in BPD. The relationship between circABCC4 level and BPD clinicopathological characteristics was analyzed. The function of circABCC4 was evaluated by performing CCK-8 and apoptosis analysis and BPD model analysis . RNA immunoprecipitation (RIP), luciferase reporter and rescue experiments were used to elucidate the interaction between circABCC4 and miR-663a. Luciferase reporter assay and rescue experiments were used to elucidate the interaction between PLA2G6 and miR-663a. CircABCC4 and PLA2G6 levels were increased, while miR-663a levels were decreased in the BPD group, compared to the control group. MiR-663a inhibited apoptosis by repressing PLA2G6 expression, while circABCC4 enhanced the apoptosis and inhibited the proliferation of A549 cells by sponging miR-663a and increasing PLA2G6 expression. In conclusion, circABCC4 promotes the evolving of BPD by spongening miR-663a and up-regulating PLA2G6 expression, which makes circABCC4 an ideal molecular target for early diagnosis and intervention of BPD.

摘要

环状RNA(circRNA)已越来越多地被证明是一种在多种人类疾病中具有前景的新型治疗性RNA分子。然而,circRNA在支气管肺发育不良(BPD)中的作用尚未阐明。在此,从安捷伦circRNA芯片中鉴定出一种新的circRNA circABCC4,它是BPD中差异表达的circRNA。分析了circABCC4水平与BPD临床病理特征之间的关系。通过进行CCK-8和凋亡分析以及BPD模型分析来评估circABCC4的功能。采用RNA免疫沉淀(RIP)、荧光素酶报告基因和挽救实验来阐明circABCC4与miR-663a之间的相互作用。采用荧光素酶报告基因检测和挽救实验来阐明PLA2G6与miR-663a之间的相互作用。与对照组相比,BPD组中circABCC4和PLA2G6水平升高,而miR-663a水平降低。miR-663a通过抑制PLA2G6表达来抑制凋亡,而circABCC4通过海绵吸附miR-663a并增加PLA2G6表达来增强A549细胞的凋亡并抑制其增殖。总之,circABCC4通过海绵吸附miR-663a和上调PLA2G6表达促进BPD的进展,这使得circABCC4成为BPD早期诊断和干预的理想分子靶点。

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