{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:50:48Z","timestamp":1791287448122,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2161,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,10]]},"abstract":"\n \n \n MicroRNAs (miRs) are conserved, small (20-25 nucleotide) noncoding RNAs that negatively regulate expression of messenger RNAs (mRNAs) at the posttranscriptional level. Aberrant expression of certain microRNAs plays a causal role in tumorigenesis. Here, we report identification of hepatic microRNAs that are dysregulated at early stages of feeding C57BL\/6 mice choline-deficient and amino acid\u2013defined (CDAA) diet that is known to promote nonalcoholic steatohepatitis (NASH)-induced hepatocarcinogenesis after 84 weeks. Microarray analysis identified 30 hepatic microRNAs that are significantly (<\/jats:bold>\n \n P\n <\/jats:bold>\n \u2264 0.01) altered in mice fed CDAA diet for 6, 18, 32, and 65 weeks compared with those fed choline-sufficient and amino acid\u2013defined (CSAA) diet. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated up-regulation of oncogenic miR-155, miR-221\/222, and miR-21 and down-regulation of the most abundant liver-specific miR-122 at early stages of hepatocarcinogenesis. Western blot analysis showed reduced expression of hepatic phosphatase and tensin homolog (PTEN) and CCAAT\/enhancer binding protein beta (C\/EBP\u03b2), respective targets of miR-21 and miR-155, in these mice at early stages. DNA binding activity of nuclear factor kappa B (NF-\u03baB) that transactivates<\/jats:bold>\n \n miR-155\n <\/jats:bold>\n gene was significantly (<\/jats:bold>\n \n P\n <\/jats:bold>\n = 0.002) elevated in the liver nuclear extract of mice fed CDAA diet. Furthermore, the expression of miR-155, as measured by<\/jats:bold>\n \n in situ\n <\/jats:bold>\n hybridization and real-time RT-PCR, correlated with diet-induced histopathological changes in the liver. Ectopic expression of miR-155 promoted growth of hepatocellular carcinoma (HCC) cells, whereas its depletion inhibited cell growth. Notably, miR-155 was significantly (<\/jats:bold>\n \n P\n <\/jats:bold>\n = 0.0004) up-regulated in primary human HCCs with a concomitant decrease (<\/jats:bold>\n \n P\n <\/jats:bold>\n = 0.02) in C\/EBP\u03b2 level compared with matching liver tissues.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Temporal changes in microRNA profile occur at early stages of CDAA diet-induced hepatocarcinogenesis. Reciprocal regulation of specific oncomirs and their tumor suppressor targets implicate their role in NASH-induced hepatocarcinogenesis and suggest their use in the diagnosis, prognosis, and therapy of liver cancer. (Hepatology 2009.)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.23100","type":"journal-article","created":{"date-parts":[[2009,5,29]],"date-time":"2009-05-29T19:49:57Z","timestamp":1243626597000},"page":"1152-1161","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":264,"title":["Role of MicroRNA-155 at Early Stages of Hepatocarcinogenesis Induced by Choline-Deficient and Amino Acid\u2013Defined Diet in C57BL\/6 Mice\u2020"],"prefix":"10.1097","volume":"50","author":[{"given":"Bo","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmila","family":"Majumder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Nuovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huban","family":"Kutay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Volinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Schmittgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Croce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Ghoshal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samson T.","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-22-20241201","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S1535-6108(04)00058-3","article-title":"Focus on hepatocellular carcinoma.","volume":"5","author":"Bruix","year":"2004","journal-title":"Cancer Cell"},{"key":"R2-22-20241201","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: epidemiology and molecular 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