Construction of a ceRNA network and screening of potential biomarkers and molecular targets in male smokers with chronic obstructive pulmonary disease

Jihua Zhang; Shuanglan Xu; Jie Liu; Ting Liu; Zeqin Fan; Yunchun Zhou; Jorina Basnet; Liqiong Zhang; Xiao Li; Jiao Yang; Xiqian Xing

doi:10.3389/fgene.2024.1376721

Construction of a ceRNA network and screening of potential biomarkers and molecular targets in male smokers with chronic obstructive pulmonary disease

Front Genet. 2024 Jun 12:15:1376721. doi: 10.3389/fgene.2024.1376721. eCollection 2024.

Authors

Jihua Zhang^#¹, Shuanglan Xu^#², Jie Liu^#³, Ting Liu^#^{2

4}, Zeqin Fan², Yunchun Zhou¹, Jorina Basnet², Liqiong Zhang¹, Xiao Li¹, Jiao Yang⁵, Xiqian Xing²

Affiliations

¹ Department of Respiratory Medicine, The People's Hospital of Yuxi City, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, China.
² Key Laboratory of Respiratory Disease Research of Department of Education of Yunnan Province, Department of Respiratory Medicine, The Affiliated Hospital of Yunnan University, The Second People's Hospital of Yunnan Province, Kunming, Yunnan, China.
³ Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
⁴ Graduate School, Kunming Medical University, Kunming, Yunnan, China.
⁵ First Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

^# Contributed equally.

Abstract

Background: Circular RNAs (circRNAs) play an important role in the occurrence and development of diseases. However, the role of circRNAs in male smokers with chronic obstructive pulmonary disease (COPD) remains unclear.

Methods: Stable COPD patients and healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were extracted. After high-throughput RNA sequencing (RNA-Seq) of PBMCs, a bioinformatics method was used to analyse differentially expressed (DE) circRNAs (DEcircRNAs) and mRNAs (DEmRNAs).

Results: Total of 114 DEcircRNAs and 58 DEmRNAs were identified. Functional enrichment analysis showed that processes related to COPD include the regulation of interleukin (IL)-18, IL-5 and the NLRP3 inflammasome; differentiation of T helper type 1 (Th1), Th2, and Th17 cells, and the AMPK, Wnt, JAK-STAT, and PI3K-Akt signalling pathways. In the protein-protein interaction (PPI) network, the core genes were MYO16, MYL4, SCN4A, NRCAM, HMCN1, MYOM2, and IQSEC3. Small-molecule prediction results revealed potential drugs for the COPD treatment. Additionally, the circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network was constructed.

Conclusion: This study identified a set of dysregulated circRNAs and mRNAs and revealed potentially important genes, pathways, new small-molecule drugs and ceRNA regulatory networks in male smokers with COPD. These circRNAs might be prospective biomarkers or potential molecular targets of the ceRNA mechanism for COPD.

Keywords: biomarker; chronic obstructive pulmonary disease; circular RNAs; competitive endogenous RNA; target.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by a grant from the National Natural Science Foundation of China (No. 82160016), Famous Doctors of High-level Talent Training Support Program of Yunnan Province (No. YNWR-MY-2020-013), the Special and Joint Program of the Yunnan Provincial Science and Technology Department and Kunming Medical University (No. 202201AY070001-265 and 202301AY070001-189), and Yunnan Provincial Innovation Team for Respiratory and Pulmonary Circulation Diseases (No. 202405AS350018).