{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:33:54Z","timestamp":1790051634899,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,11,5]],"date-time":"2012-11-05T00:00:00Z","timestamp":1352073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>); however, the mechanisms by which alcohol promotes <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection remain obscure. The liver\u2010specific micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010122 (miR\u2010122) regulates <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replication and expression of host genes, including Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1. Here, we hypothesized that alcohol regulates mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 expression and thereby modulates <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> replication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>6\/<jats:styled-content style=\"fixed-case\">JFH<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>uh\u20107.5 model of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection was used in this study. Real\u2010time quantitative <jats:styled-content style=\"fixed-case\">polymerase chain reaction<\/jats:styled-content>, Western blotting, electrophoretic mobility shift assay, and confocal microscopy were used for experimental analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that acute alcohol exposure (25\u00a0mM) significantly increased intracellular <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> as well as mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 levels in <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>uh\u20107.5 and <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>uh\u20107.5\/<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>1 expressing cells in the presence and absence of <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>6\/<jats:styled-content style=\"fixed-case\">JFH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. Expression of the mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 target, Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1, was inhibited by alcohol both in <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>6\/<jats:styled-content style=\"fixed-case\">JFH<\/jats:styled-content>\u2010infected and uninfected <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>uh\u20107.5 cells. The use of a mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 inhibitor increased Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1 expression and prevented the alcohol\u2010induced increase in <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> and protein levels, suggesting a mechanistic role for alcohol\u2010induced mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>122 in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replication. We discovered that si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated silencing of Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1 significantly increased intracellular <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> levels compared with controls, suggesting a mechanistic role for Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1 in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replication. Alcohol\u2010induced increase in mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 was associated with increased nuclear translocation and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> binding of the nuclear regulatory factor\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> and could be prevented by <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our novel data indicate a mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122\u2010mediated mechanism for alcohol increasing <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> replication. We show for the first time that Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1, a mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 target gene, has regulatory effects on <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replication and that alcohol increases <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replication by regulating mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010122 and Cyclin <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12005","type":"journal-article","created":{"date-parts":[[2012,11,5]],"date-time":"2012-11-05T16:11:30Z","timestamp":1352131890000},"page":"599-608","source":"Crossref","is-referenced-by-count":37,"title":["Alcohol Facilitates <scp>HCV RNA<\/scp> Replication Via Up\u2010Regulation of mi<scp>R<\/scp>\u2010122 Expression and Inhibition of Cyclin <scp>G<\/scp>1 in Human Hepatoma Cells"],"prefix":"10.1111","volume":"37","author":[{"given":"Wei","family":"Hou","sequence":"first","affiliation":[{"name":"University of Massachusetts Medical School Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence N.","family":"Bukong","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kodys","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyongyi","family":"Szabo","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School Worcester 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