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

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

PMC · DOI: 10.3389/fgene.2024.1376721 · Frontiers in Genetics · 2024-06-12

## TL;DR

This study explores how circular RNAs and mRNAs are involved in COPD in male smokers, identifying potential biomarkers and drug targets.

## Contribution

The study constructs a ceRNA network and identifies novel biomarkers and molecular targets specific to male smokers with COPD.

## Key findings

- 114 differentially expressed circRNAs and 58 mRNAs were identified in COPD patients.
- Key pathways include IL-18, IL-5, NLRP3 inflammasome, and T helper cell differentiation.
- Potential drugs and a ceRNA regulatory network were predicted for COPD treatment.

## Abstract

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.

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).

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.

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.

## Linked entities

- **Genes:** MYO16 (myosin XVI) [NCBI Gene 23026], MYL4 (myosin light chain 4) [NCBI Gene 4635], SCN4A (sodium voltage-gated channel alpha subunit 4) [NCBI Gene 6329], NRCAM (neuronal cell adhesion molecule) [NCBI Gene 4897], HMCN1 (hemicentin 1) [NCBI Gene 83872], MYOM2 (myomesin 2) [NCBI Gene 9172], IQSEC3 (IQ motif and Sec7 domain ArfGEF 3) [NCBI Gene 440073]
- **Diseases:** chronic obstructive pulmonary disease (MONDO:0005002), COPD (MONDO:0005002)

## Full-text entities

- **Genes:** HMCN1 (hemicentin 1) [NCBI Gene 83872] {aka ARMD1, FBLN6, FIBL-6, FIBL6}, MYOM2 (myomesin 2) [NCBI Gene 9172] {aka TTNAP}, SCN4A (sodium voltage-gated channel alpha subunit 4) [NCBI Gene 6329] {aka CMS16, CMYO22A, CMYP22A, HOKPP2, HYKPP, HYPP}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, NRCAM (neuronal cell adhesion molecule) [NCBI Gene 4897] {aka NEDNMS}, MYL4 (myosin light chain 4) [NCBI Gene 4635] {aka ALC1, AMLC, GT1, PRO1957}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, IQSEC3 (IQ motif and Sec7 domain ArfGEF 3) [NCBI Gene 440073], MYO16 (myosin XVI) [NCBI Gene 23026] {aka MYAP3, MYR8, Myo16b, NYAP3, PPP1R107}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}
- **Diseases:** COPD (MESH:D029424)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11199688/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC11199688/full.md

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Source: https://tomesphere.com/paper/PMC11199688