Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells

Yen-Hung Wu; I-Jeng Yeh; Nam Nhut Phan; Meng-Chi Yen; Jui-Hsiang Hung; Chung-Chieh Chiao; Chien-Fu Chen; Zhengda Sun; Hui-Ping Hsu; Chih-Yang Wang; Ming-Derg Lai

Journal of Microbiology, Immunology and Infection (Oct 2021)

Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells

Yen-Hung Wu,
I-Jeng Yeh,
Nam Nhut Phan,
Meng-Chi Yen,
Jui-Hsiang Hung,
Chung-Chieh Chiao,
Chien-Fu Chen,
Zhengda Sun,
Hui-Ping Hsu,
Chih-Yang Wang,
Ming-Derg Lai

Affiliations

Yen-Hung Wu: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
I-Jeng Yeh: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Nam Nhut Phan: NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam
Meng-Chi Yen: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Jui-Hsiang Hung: Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
Chung-Chieh Chiao: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
Chien-Fu Chen: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
Zhengda Sun: Kaiser Permanente, Northern California Regional Laboratories, The Permanente Medical Group, 1725 Eastshore Hwy, Berkeley, CA 94710, USA
Hui-Ping Hsu: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN37232, USA; Corresponding author. Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Chih-Yang Wang: Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Corresponding author. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Ming-Derg Lai: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 70101, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Corresponding author. Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 70101, Taiwan.

Journal volume & issue: Vol. 54, no. 5
pp. 845 – 857

Abstract

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Background: Pathogenic coronaviruses include Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. These viruses have induced outbreaks worldwide, and there are currently no effective medications against them. Therefore, there is an urgent need to develop potential drugs against coronaviruses. Methods: High-throughput technology is widely used to explore differences in messenger (m)RNA and micro (mi)RNA expression profiles, especially to investigate protein–protein interactions and search for new therapeutic compounds. We integrated miRNA and mRNA expression profiles in MERS-CoV-infected cells and compared them to mock-infected controls from public databases. Results: Through the bioinformatics analysis, there were 251 upregulated genes and eight highly differentiated miRNAs that overlapped in the two datasets. External validation verified that these genes had high expression in MERS-CoV-infected cells, including RC3H1, NF-κB, CD69, TNFAIP3, LEAP-2, DUSP10, CREB5, CXCL2, etc. We revealed that immune, olfactory or sensory system-related, and signal-transduction networks were discovered from upregulated mRNAs in MERS-CoV-infected cells. In total, 115 genes were predicted to be related to miRNAs, with the intersection of upregulated mRNAs and miRNA-targeting prediction genes such as TCF4, NR3C1, and POU2F2. Through the Connectivity Map (CMap) platform, we suggested potential compounds to use against MERS-CoV infection, including diethylcarbamazine, harpagoside, bumetanide, enalapril, and valproic acid. Conclusions: The present study illustrates the crucial roles of miRNA-mRNA interacting networks in MERS-CoV-infected cells. The genes we identified are potential targets for treating MERS-CoV infection; however, these could possibly be extended to other coronavirus infections.

Published in Journal of Microbiology, Immunology and Infection

ISSN: 1684-1182 (Print)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Science: Microbiology
Website: https://www.sciencedirect.com/journal/journal-of-microbiology-immunology-and-infection

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