Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation.
Identifieur interne : 000251 ( Main/Exploration ); précédent : 000250; suivant : 000252Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation.
Auteurs : Xi Zhang [République populaire de Chine] ; Hin Chu [République populaire de Chine] ; Lei Wen [République populaire de Chine] ; Huiping Shuai [République populaire de Chine] ; Dong Yang [République populaire de Chine] ; Yixin Wang [République populaire de Chine] ; Yuxin Hou [République populaire de Chine] ; Zheng Zhu [République populaire de Chine] ; Shuofeng Yuan [République populaire de Chine] ; Feifei Yin [République populaire de Chine] ; Jasper Fuk-Woo Chan [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine]Source :
- Emerging microbes & infections [ 2222-1751 ] ; 2020.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN messager (métabolisme), Analyse de profil d'expression de gènes, Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Expression des gènes, Humains, Interférence par ARN, Lignée cellulaire tumorale, Petit ARN interférent, Réplication virale, Réseaux de régulation génique, Transcription génétique, microARN (génétique), microARN (métabolisme).
- MESH :
- génétique : ARN messager, microARN.
- métabolisme : ARN messager, microARN.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- Analyse de profil d'expression de gènes, Expression des gènes, Humains, Interférence par ARN, Lignée cellulaire tumorale, Petit ARN interférent, Réplication virale, Réseaux de régulation génique, Transcription génétique.
English descriptors
- KwdEn :
- Cell Line, Tumor, Gene Expression, Gene Expression Profiling, Gene Regulatory Networks, Humans, MicroRNAs (genetics), MicroRNAs (metabolism), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (physiology), RNA Interference, RNA, Circular (genetics), RNA, Circular (metabolism), RNA, Messenger (genetics), RNA, Messenger (metabolism), RNA, Small Interfering, Transcription, Genetic, Virus Replication.
- MESH :
- chemical , genetics : MicroRNAs, RNA, Circular, RNA, Messenger.
- chemical , metabolism : MicroRNAs, RNA, Circular, RNA, Messenger.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- Cell Line, Tumor, Gene Expression, Gene Expression Profiling, Gene Regulatory Networks, Humans, RNA Interference, RNA, Small Interfering, Transcription, Genetic, Virus Replication.
Abstract
Circular RNAs (circRNAs) are an integral component of the host competitive endogenous RNA (ceRNA) network. These noncoding RNAs are characterized by their unique splicing reactions to form covalently closed loop structures and play important RNA regulatory roles in cells. Recent studies showed that circRNA expressions were perturbed in viral infections and circRNAs might serve as potential antiviral targets. We investigated the host ceRNA network changes and biological relevance of circRNAs in human lung adenocarcinoma epithelial (Calu-3) cells infected with the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). A total of ≥49337 putative circRNAs were predicted. Among the 7845 genes which generated putative circRNAs, 147 (1.9%) of them each generated ≥30 putative circRNAs and were involved in various biological, cellular, and metabolic processes, including viral infections. Differential expression (DE) analysis showed that the proportion of DE circRNAs significantly (P < 0.001) increased at 24 h-post infection. These DE circRNAs were clustered into 4 groups according to their time-course expression patterns and demonstrated inter-cluster and intra-cluster variations in the predicted functions of their host genes. Our comprehensive circRNA-miRNA-mRNA network identified 7 key DE circRNAs involved in various biological processes upon MERS-CoV infection. Specific siRNA knockdown of two selected DE circRNAs (circFNDC3B and circCNOT1) significantly reduced MERS-CoV load and their target mRNA expression which modulates various biological pathways, including the mitogen-activated protein kinase (MAPK) and ubiquitination pathways. These results provided novel insights into the ceRNA network perturbations, biological relevance of circRNAs, and potential host-targeting antiviral strategies for MERS-CoV infection.
DOI: 10.1080/22221751.2020.1738277
PubMed: 32223537
Affiliations:
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Le document en format XML
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sort="Zhu, Zheng" uniqKey="Zhu Z" first="Zheng" last="Zhu">Zheng Zhu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yuan, Shuofeng" sort="Yuan, Shuofeng" uniqKey="Yuan S" first="Shuofeng" last="Yuan">Shuofeng Yuan</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country 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of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Wen, Lei" sort="Wen, Lei" uniqKey="Wen L" first="Lei" last="Wen">Lei Wen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Shuai, Huiping" sort="Shuai, Huiping" uniqKey="Shuai H" first="Huiping" last="Shuai">Huiping Shuai</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Dong" sort="Yang, Dong" uniqKey="Yang D" first="Dong" last="Yang">Dong Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yixin" sort="Wang, Yixin" uniqKey="Wang Y" first="Yixin" last="Wang">Yixin Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Hou, Yuxin" sort="Hou, Yuxin" uniqKey="Hou Y" first="Yuxin" last="Hou">Yuxin Hou</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Zheng" sort="Zhu, Zheng" uniqKey="Zhu Z" first="Zheng" last="Zhu">Zheng Zhu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yuan, Shuofeng" sort="Yuan, Shuofeng" uniqKey="Yuan S" first="Shuofeng" last="Yuan">Shuofeng Yuan</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yin, Feifei" sort="Yin, Feifei" uniqKey="Yin F" first="Feifei" last="Yin">Feifei Yin</name><affiliation wicri:level="1"><nlm:affiliation>Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, People's Republic of China, and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, People's Republic of China, and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></analytic><series><title level="j">Emerging microbes & infections</title><idno type="eISSN">2222-1751</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line, Tumor</term><term>Gene Expression</term><term>Gene Expression Profiling</term><term>Gene Regulatory Networks</term><term>Humans</term><term>MicroRNAs (genetics)</term><term>MicroRNAs (metabolism)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>RNA Interference</term><term>RNA, Circular (genetics)</term><term>RNA, Circular (metabolism)</term><term>RNA, Messenger (genetics)</term><term>RNA, Messenger (metabolism)</term><term>RNA, Small Interfering</term><term>Transcription, Genetic</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>Analyse de profil d'expression de gènes</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Expression des gènes</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Petit ARN interférent</term><term>Réplication virale</term><term>Réseaux de régulation génique</term><term>Transcription génétique</term><term>microARN (génétique)</term><term>microARN (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>MicroRNAs</term><term>RNA, Circular</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>MicroRNAs</term><term>RNA, Circular</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>microARN</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>microARN</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Gene Expression</term><term>Gene Expression Profiling</term><term>Gene Regulatory Networks</term><term>Humans</term><term>RNA Interference</term><term>RNA, Small Interfering</term><term>Transcription, Genetic</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Expression des gènes</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Petit ARN interférent</term><term>Réplication virale</term><term>Réseaux de régulation génique</term><term>Transcription génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Circular RNAs (circRNAs) are an integral component of the host competitive endogenous RNA (ceRNA) network. These noncoding RNAs are characterized by their unique splicing reactions to form covalently closed loop structures and play important RNA regulatory roles in cells. Recent studies showed that circRNA expressions were perturbed in viral infections and circRNAs might serve as potential antiviral targets. We investigated the host ceRNA network changes and biological relevance of circRNAs in human lung adenocarcinoma epithelial (Calu-3) cells infected with the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). A total of ≥49337 putative circRNAs were predicted. Among the 7845 genes which generated putative circRNAs, 147 (1.9%) of them each generated ≥30 putative circRNAs and were involved in various biological, cellular, and metabolic processes, including viral infections. Differential expression (DE) analysis showed that the proportion of DE circRNAs significantly (<i>P</i> < 0.001) increased at 24 h-post infection. These DE circRNAs were clustered into 4 groups according to their time-course expression patterns and demonstrated inter-cluster and intra-cluster variations in the predicted functions of their host genes. Our comprehensive circRNA-miRNA-mRNA network identified 7 key DE circRNAs involved in various biological processes upon MERS-CoV infection. Specific siRNA knockdown of two selected DE circRNAs (circFNDC3B and circCNOT1) significantly reduced MERS-CoV load and their target mRNA expression which modulates various biological pathways, including the mitogen-activated protein kinase (MAPK) and ubiquitination pathways. These results provided novel insights into the ceRNA network perturbations, biological relevance of circRNAs, and potential host-targeting antiviral strategies for MERS-CoV infection.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Shenzhen</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Xi" sort="Zhang, Xi" uniqKey="Zhang X" first="Xi" last="Zhang">Xi Zhang</name></noRegion><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><name sortKey="Hou, Yuxin" sort="Hou, Yuxin" uniqKey="Hou Y" first="Yuxin" last="Hou">Yuxin Hou</name><name sortKey="Shuai, Huiping" sort="Shuai, Huiping" uniqKey="Shuai H" first="Huiping" last="Shuai">Huiping Shuai</name><name sortKey="Wang, Yixin" sort="Wang, Yixin" uniqKey="Wang Y" first="Yixin" last="Wang">Yixin Wang</name><name sortKey="Wen, Lei" sort="Wen, Lei" uniqKey="Wen L" first="Lei" last="Wen">Lei Wen</name><name sortKey="Yang, Dong" sort="Yang, Dong" uniqKey="Yang D" first="Dong" last="Yang">Dong Yang</name><name sortKey="Yin, Feifei" sort="Yin, Feifei" uniqKey="Yin F" first="Feifei" last="Yin">Feifei Yin</name><name sortKey="Yuan, Shuofeng" sort="Yuan, Shuofeng" uniqKey="Yuan S" first="Shuofeng" last="Yuan">Shuofeng Yuan</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><name sortKey="Zhu, Zheng" sort="Zhu, Zheng" uniqKey="Zhu Z" first="Zheng" last="Zhu">Zheng Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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