{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:02:26Z","timestamp":1760151746516,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860357"],"award-info":[{"award-number":["81860357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Province, China","award":["YNWR-QNBJ-2019-178"],"award-info":[{"award-number":["YNWR-QNBJ-2019-178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hand, foot and mouth disease (HFMD) caused by Coxsackievirus Group B5 (CVB5) is one of the most common herpetic diseases in human infants and children. The pathogenesis of CVB5 remains unknown. Circular RNAs (CircRNAs), as novel noncoding RNAs, have been shown to play a key role in many pathogenic processes in different species; however, their functions during the process of CVB5 infection remain unclear. In the present study, we investigated the expression profiles of circRNAs using RNA sequencing technology in CVB5-infected and mock-infected human rhabdomyosarcoma cells (CVB5 virus that had been isolated from clinical specimens). In addition, several differentially expressed circRNAs were validated by RT-qPCR. Moreover, the innate immune responses related to circRNA-miRNA-mRNA interaction networks were constructed and verified. A total of 5461 circRNAs were identified at different genomic locations in CVB5 infections and controls, of which 235 were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that the differentially expressed circRNAs were principally involved in specific signaling pathways related to ErbB, TNF, and innate immunity. We further predicted that novel_circ_0002006 might act as a molecular sponge for miR-152-3p through the IFN-I pathway to inhibit CVB5 replication, and that novel_circ_0001066 might act as a molecular sponge for miR-29b-3p via the NF-\u03baB pathway and for the inhibition of CVB5 replication. These findings will help to elucidate the biological functions of circRNAs in the progression of CVB5-related HFMD and identify prospective biomarkers and therapeutic targets for this disease.<\/jats:p>","DOI":"10.3390\/ijms23094628","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"4628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bioinformatics and Screening of a Circular RNA-microRNA-mRNA Regulatory Network Induced by Coxsackievirus Group B5 in Human Rhabdomyosarcoma Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiying","family":"Teng","sequence":"additional","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Ou","sequence":"additional","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical School, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.meegid.2012.10.016","article-title":"Picornavirus and enterovirus diversity with associated human diseases","volume":"14","author":"Tapparel","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/jmv.25393","article-title":"Ongoing change of severe hand, foot, and mouth disease pathogens in Yunnan, China, 2012 to 2016","volume":"91","author":"Du","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s00705-019-04356-0","article-title":"Molecular epidemiology of enterovirus from children with herpangina or hand, foot, and mouth disease in Hangzhou, 2016","volume":"164","author":"Li","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00430-016-0465-y","article-title":"Hand, foot and mouth disease (HFMD): Emerging epidemiology and the need for a vaccine strategy","volume":"205","author":"Aswathyraj","year":"2016","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e01125-17","DOI":"10.1128\/genomeA.01125-17","article-title":"Genome Sequences of Coxsackievirus B5 Isolates from Two Children with Meningitis in Australia","volume":"5","author":"Huang","year":"2017","journal-title":"Genome Announc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijid.2014.02.005","article-title":"An outbreak of aseptic meningitis caused by a distinct lineage of coxsackievirus B5 in China","volume":"23","author":"Liu","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.7150\/ijbs.22531","article-title":"Circular RNAs: A novel type of non-coding RNA and their potential implications in antiviral immunity","volume":"13","author":"Wang","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_8","first-page":"1032","article-title":"Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges","volume":"15","author":"Jost","year":"2018","journal-title":"RNA Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0101721","DOI":"10.1128\/mBio.01017-21","article-title":"A Novel Intronic Circular RNA Antagonizes Influenza Virus by Absorbing a microRNA That Degrades CREBBP and Accelerating IFN-\u03b2 Production","volume":"12","author":"Qu","year":"2021","journal-title":"mBio"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2020.1790198","article-title":"The emerging role and significance of circular RNAs in viral infections and antiviral immune responses: Possible implication as theranostic agents","volume":"18","author":"Awan","year":"2020","journal-title":"RNA Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.virol.2019.01.014","article-title":"Identification of virus-encoded circular RNA","volume":"529","author":"Huang","year":"2019","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.7150\/ijms.45637","article-title":"Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer","volume":"17","author":"Wang","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"198205","DOI":"10.1016\/j.virusres.2020.198205","article-title":"The role of circular RNAs in viral infection and related diseases","volume":"291","author":"Xie","year":"2020","journal-title":"Virus Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"779919","DOI":"10.3389\/fcimb.2021.779919","article-title":"The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase Front","volume":"11","author":"Yang","year":"2022","journal-title":"Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1007\/s00705-021-05190-z","article-title":"circRNA expression patterns and circRNA-miRNA-mRNA networks during CV-A16 infection of SH-SY5Y cells","volume":"166","author":"Hu","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"198502","DOI":"10.1016\/j.virusres.2021.198502","article-title":"Comprehensive analysis of the circRNA expression profile and circRNA-miRNA-mRNA network in the pathogenesis of EV-A71 infection","volume":"303","author":"Hu","year":"2021","journal-title":"Virus Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/s41467-021-21456-1","article-title":"E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF","volume":"12","author":"Gao","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/s41467-020-14948-z","article-title":"Regulation of the linear ubiquitination of STAT1 controls antiviral interferon signaling","volume":"11","author":"Zuo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/hep4.1821","article-title":"HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta","volume":"6","author":"Sandmann","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110373","DOI":"10.1016\/j.celrep.2022.110373","article-title":"TBK1-METTL3 axis facilitates antiviral immunity","volume":"38","author":"Chen","year":"2022","journal-title":"Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104290","DOI":"10.1016\/j.dci.2021.104290","article-title":"Porcine TRIM35 positively regulate TRAF3-mediated IFN-\u03b2 production and inhibit Japanese encephalitis virus replication","volume":"127","author":"Li","year":"2021","journal-title":"Dev. Comp. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/febs.13713","article-title":"MicroRNA 152 regulates hepatic glycogenesis by targeting PTEN","volume":"283","author":"Wang","year":"2016","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1002\/jmv.26629","article-title":"Identification of miRNAs associated with dendritic cell dysfunction during acute and chronic hepatitis B virus infection","volume":"93","author":"Singh","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s13046-019-1390-x","article-title":"Long non-coding RNA LINC00174 promotes glycolysis and tumor progression by regulating miR-152-3p\/SLC2A1 axis in glioma","volume":"38","author":"Shi","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13046-021-02122-2","article-title":"Mutant NPM1-regulated lncRNA HOTAIRM1 promotes leukemia cell autophagy and proliferation by targeting EGR1 and ULKJ","volume":"40","author":"Jing","year":"2021","journal-title":"Exp. Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, Y., Ashraf, U., Chen, Z., Zhou, D., Imran, M., Ye, J., Chen, H., and Cao, S. (2020). Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response. BMC Genom., 21.","DOI":"10.1186\/s12864-020-06822-5"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12985-021-01717-7","article-title":"Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response","volume":"18","author":"Wu","year":"2021","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/bib\/bbx014","article-title":"Circular RNA identification based on multiple seed matching","volume":"19","author":"Gao","year":"2017","journal-title":"Brief. Bioinform."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:38Z","timestamp":1760137118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,22]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23094628"],"URL":"https:\/\/doi.org\/10.3390\/ijms23094628","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,4,22]]}}}