Cigarette smoke extract alters genome-wide profiles of circular RNAs and mRNAs in primary human small airway epithelial cells.

Ni Zeng,Yanqiu Wu,Fuqiang Wen,Jiangyue Qin,Zhicheng Yuan,Lijuan Gao,Mei Chen,Tao Wang,Yongchun Shen,Lei Chen

doi:10.1111/jcmm.14436

Abstract

As a novel kind of non‐coding RNA, circular RNAs (circRNAs) were involved in various biological processes. However, the role of circRNAs in the developmental process of chronic obstructive pulmonary disease (COPD) is still unclear. In the present study, by using a cell model of COPD in primary human small airway epithelial cells (HSAECs) treated with or without cigarette smoke extract (CSE), we uncovered 4,379 previously unknown circRNAs in human cells and 903 smoke‐specific circRNAs, with the help of RNA‐sequencing and bioinformatic analysis. Moreover, 3,872 up‐ and 4,425 down‐regulated mRNAs were also identified under CSE stimulation. Furthermore, a putative circRNA‐microRNA‐mRNA network was constructed for in‐depth mechanism exploration, which indicated that differentially expressed circRNAs could influence expression of some key genes that participate in response to pentose phosphate pathway, ATP‐binding cassette (ABC) transporters, glycosaminoglycan biosynthesis pathway and cancer‐related pathways. Our research indicated that cigarette smoke had an influence on the biogenesis of circRNAs and mRNAs. CircRNAs might be involved in the response to CSE in COPD through the circRNA‐mediated ceRNA networks.

Highlights

Associated with a high prevalence and related disability and mor‐ tality, chronic obstructive pulmonary disease (COPD) has be‐ come a worldwide public health challenge
We investigated the expression patterns of cir‐ cRNAs and mRNAs under cigarette smoking stimulation, a major environmental contributor to COPD, in primary human small airway epithelial cells (HSAECs), to explore the possible underlying molecu‐ lar regulation mechanism of circRNAs in COPD
To construct a putative circRNA‐mediated competing endogenous RNA network, we identified all microRNA target‐ ing circRNA and all miRNA targeting gene based on TargetScan and miRanda

Summary

| INTRODUCTION

Associated with a high prevalence and related disability and mor‐ tality, chronic obstructive pulmonary disease (COPD) has be‐ come a worldwide public health challenge. Abundant circRNAs have been discovered in various cells, be‐ cause of the help of high throughput sequencing technologies and bioinformatic analysis.[8,10] Subsequent reports revealed that cir‐ cRNAs may be involved in several cellular and developmental pro‐ cess of some diseases, such as prion diseases, neurological disorders, atherosclerotic vascular disease risk, as well as different malignant tumours.[6,7,11,12] It is reported that circRNAs could function as po‐ tential disease biomarkers in human saliva and as biomarkers for non‐small cell lung cancer and ageing.[13,14,15] the possible involvement of circRNAs in the pathogenesis of COPD remains elu‐ sive. We investigated the expression patterns of cir‐ cRNAs and mRNAs under cigarette smoking stimulation, a major environmental contributor to COPD, in primary human small airway epithelial cells (HSAECs), to explore the possible underlying molecu‐ lar regulation mechanism of circRNAs in COPD

| METHODS AND MATERIALS

| DISCUSSION

| CONCLUSION