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

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

doi:10.3389/fcell.2020.585541

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 in vitro and BPD model analysis in vivo. 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.

Highlights

Bronchopulmonary dysplasia (BPD) is a chronic lung disease with high incidence and mortality in premature infants who require mechanical ventilation (Hwang and Rehan, 2018; Tracy and Berkelhamer, 2019)
The results showed that circABCC4 expression was up-regulated under bronchopulmonary dysplasia (BPD) group, compared with those in control group
Its fold change was not the largest, the circABCC4 expression showed the strongest relevance to BPD among all the circRNAs (Figure 3A)

Summary

Introduction

Bronchopulmonary dysplasia (BPD) is a chronic lung disease with high incidence and mortality in premature infants who require mechanical ventilation (Hwang and Rehan, 2018; Tracy and Berkelhamer, 2019). CircRNAs are non-coding RNAs bearing a covalently closed continuous loop between 5 - and 3 -ends (Conn et al, 2015). This circular structure endows circRNAs with a high stability in different species. There are scarce reports of circRNAs in the animal model of BPD, and previous findings are mainly made through sequencing analyses. There are few studies on circABCC4, mainly focusing on cancer (Huang et al, 2019). Studies have found that circABCC4 is highly expressed in lung adenocarcinoma and prostate cancer (Huang et al, 2019; Liu et al, 2020). Inhibition of MRP4 can significantly reduce sepsis-induced ALI (Xia et al, 2019)

Methods

Results

Conclusion