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ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease

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Abstract

The continued spread of SARS-CoV-2 has presented unprecedented obstacles to the worldwide public health system. Especially, individuals with chronic obstructive pulmonary disease (COPD) are at a heightened risk of contracting SARS-CoV-2 infection due to their pre-existing respiratory symptoms that are not well-managed. However, the viral mechanism of affecting the expression of host genes, COPD progression, and prognosis is not clear yet.

This study integrated the differential expression information of COPD patients and then calculated the correlation between mRNAs and miRNAs to construct a COPD-specific ceRNA network. The DEGs of individuals with SARS-CoV-2 infection and anticipated miRNAs and their targets were analyzed in 9 SARS-CoV-2 sequences from different geographic locations. Furthermore, combining the experimentally validated miRNAs and genes, the regulatory miRNA-mRNA relationships were identified. All the regulatory relationships were integrated into the COPD-specific network and the network modules were explored to get insight into the functional mechanism of SARS-CoV-2 infection in COPD patients.

A higher proportion of DEGs compete with the same miRNA suggesting a higher expression of genes in the COPD-specific ceRNA network. Hsa-miR-21-3p is the largest connected point in the network, but the proportion of genes upregulated by hsa-miR-21-3p is low (P = 0.1406). This indicates that the regulatory relationship of competitive inhibition has little effect on has-miR-21, and the high expression pattern is a poor prognostic factor in COPD. Hsa-miR-15a-5p is the most significant miRNA with the highest proportion of DEGs. And ANXA2P3 is the only gene in the COPD ceRNA network that interferes with hsa-miR-15a-5p. In addition, we found that has-miR-1184- and has-miR-99-cored modules were significant, and genes ZDHHC18, PCGF3, and KIAA0319L interacting with them were all associated with COPD prognosis, and high expression of these genes could lead to poor prognosis in COPD.

The key regulators such as miR-21, miR-15a, ANXA2P3, ZDHHC18, PCGF3, and KIAA0319L can be used as prognostic biomarkers for early intervention in COPD with SARS-CoV-2 infection.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ceRNA:

Competing endogenous ribonucleic acid

COPD:

Chronic obstructive pulmonary disease

SARS-CoV-2:

Severe acquired respiratory syndrome coronavirus 2

miRNA:

MicroRNA

DEGs:

Differentially expressed genes

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Acknowledgements

We are thankful to Dr. Lindong Yuan, for critically editing the current manuscript.

Funding

This work was funded by the 2021 Annual Science and Technology Development Plan of Shandong Geriatric Society (LKJGG2021W070) and Scientific Research Fund Project of Hebei Provincial Health Commission (20231071).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care, The First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang City, 050000, Hebei Province, China

    Lihai Zhang

  2. Joint Laboratory of Translational Medicine, Liaocheng People’s Hospital, No.67, Dongchang West Road, Liaocheng City, 252000, China

    **aodong Jia

  3. Respiratory Medicine, Jiyang District People’s Hospital, No.9, **nyuan Street, Jiyang District, **an, 251400, Shandong Province, China

    Zhipeng Zhang

  4. Department of Respiratory and Critical Care Medicine, Liaocheng People’s Hospital, No.67, Dongchang West Road, Liaocheng City, 252000, China

    Tong Yu & Lindong Yuan

  5. Department of Geriatrics, First Hospital of Hebei Medical University, No.89, Donggang Road, Shijiazhuang City, 050000, Hebei Province, China

    Zhangyan Geng

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  1. Lihai Zhang
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  2. **aodong Jia
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Contributions

LY leads the study design and the overall progress. LZ performed the COPD-related data collection and analysis. ZZ performed the COPD-related data collection and analysis. XJ performed the COPD-related data collection and analysis. TY mainly taken part in the SARS-CoV-2 sequences retrieving and phylogenetic analysis. ZG mainly taken part in the SARS-CoV-2 sequences retrieving and phylogenetic analysis. LY wrote and polished the manuscripts. TY wrote and polished the manuscripts. ZG wrote and polished the manuscripts.

Corresponding author

Correspondence to Lindong Yuan.

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The study was reviewed and approved by the National Center for Health Statistics Ethics Review Board (Approval Number: 20220611). All authors have their consent to participate.

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Zhang, L., Jia, X., Zhang, Z. et al. ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease. Appl Biochem Biotechnol 196, 4303–4316 (2024). https://doi.org/10.1007/s12010-023-04773-7

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