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

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, th...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:Journal of Microbiology, Immunology and Infection
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S168411822100058X
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author 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
author_facet 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
author_sort Yen-Hung Wu
collection DOAJ
description 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.
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spelling doaj.art-7e6444b82eac4c1286777a043bf79e7a2022-12-21T21:27:49ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822021-10-01545845857Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cellsYen-Hung Wu0I-Jeng Yeh1Nam Nhut Phan2Meng-Chi Yen3Jui-Hsiang Hung4Chung-Chieh Chiao5Chien-Fu Chen6Zhengda Sun7Hui-Ping Hsu8Chih-Yang Wang9Ming-Derg Lai10Department 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, TaiwanDepartment 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, TaiwanNTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City, Viet NamDepartment 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, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 71710, TaiwanSchool of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, TaiwanSchool of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, TaiwanKaiser Permanente, Northern California Regional Laboratories, The Permanente Medical Group, 1725 Eastshore Hwy, Berkeley, CA 94710, USADepartment 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.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.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.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.http://www.sciencedirect.com/science/article/pii/S168411822100058XCoronavirusMiddle East respiratory syndrome coronavirus (MERS-CoV)miRNABioinformaticsConnectivity mapLung adenocarcinoma
spellingShingle 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
Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
Journal of Microbiology, Immunology and Infection
Coronavirus
Middle East respiratory syndrome coronavirus (MERS-CoV)
miRNA
Bioinformatics
Connectivity map
Lung adenocarcinoma
title Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
title_full Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
title_fullStr Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
title_full_unstemmed Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
title_short Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells
title_sort gene signatures and potential therapeutic targets of middle east respiratory syndrome coronavirus mers cov infected human lung adenocarcinoma epithelial cells
topic Coronavirus
Middle East respiratory syndrome coronavirus (MERS-CoV)
miRNA
Bioinformatics
Connectivity map
Lung adenocarcinoma
url http://www.sciencedirect.com/science/article/pii/S168411822100058X
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