{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:53:56Z","timestamp":1790247236254,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T00:00:00Z","timestamp":1572739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T00:00:00Z","timestamp":1572739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Hepatitis C virus (HCV) infection promotes hepatocyte growth and progress to hepatocellular carcinoma. We previously observed that HCV infection of hepatocytes transcriptionally down\u2010regulates miR\u2010181c expression through CCAAT\/enhancer binding protein \u03b2 (C\/EBP\u2010\u03b2). Here, we examined the role of miR\u2010181c in the regulation of cell cycle progression in relation to HCV infection. <jats:italic toggle=\"yes\">In silico<\/jats:italic> analysis suggested that ataxia\u2010telangiectasia mutated (ATM) protein, a protein kinase, is a direct target of miR\u2010181c. ATM is a central mediator of response for cellular DNA double\u2010strand break.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Our results demonstrated that ATM expression is higher in HCV\u2010infected hepatocytes and chronic HCV\u2010infected liver biopsy specimens. We have shown a direct interaction of miR\u2010181c with the 3\u2032 untranslated region of ATM, and the presence of ATM in miR\u2010181c\u2010associated RNA\u2010induced silencing complex. Exogenous expression of miR\u2010181c inhibited ATM expression and activation of its downstream molecules, Chk2 and Akt. On the other hand, introduction of anti\u2010miR\u2010181c restored ATM and phosphorylated Akt. Furthermore, introduction of miR\u2010181c significantly inhibited phospho\u2013cyclin\u2010dependent kinase 2 (CDK2) and cyclin\u2010A expression, arresting cell cycle progression, whereas overexpression of miR\u2010181c promoted apoptosis of HCV\u2010infected hepatocytes and can be inhibited by overexpression of ATM from a clone lacking miR\u2010181c binding sites. In addition, miR\u2010181c significantly regressed tumor growth in the xenograft human hepatocellular carcinoma mouse model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Together, our results suggest that HCV infection suppresses miR\u2010181c in hepatocytes, resulting in ATM activation and apoptosis inhibition for promotion of cell cycle progression. The results provide mechanistic insight into understanding the role of miR\u2010181c in HCV\u2010associated hepatocyte growth promotion, and may have the potential for therapeutic intervention.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.30893","type":"journal-article","created":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T10:45:40Z","timestamp":1565433940000},"page":"780-793","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Hepatitis C Virus Mediated Inhibition of miR\u2010181c Activates ATM Signaling and Promotes Hepatocyte Growth"],"prefix":"10.1097","volume":"71","author":[{"given":"Tapas","family":"Patra","sequence":"first","affiliation":[{"name":"Department of Internal Medicine,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Saint 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