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MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces <jats:italic>gfap<\/jats:italic>, the inactivation marker of HSCs, in CCl<jats:sub>4<\/jats:sub>-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-\u03baB (NF-\u03baB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-\u03baB signalling, suggesting miR-378a-3p has therapeutic potential for liver fibrosis.<\/jats:p>","DOI":"10.1038\/ncomms10993","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T10:23:17Z","timestamp":1458642197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":201,"title":["MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression"],"prefix":"10.1038","volume":"7","author":[{"given":"Jeongeun","family":"Hyun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihyung","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kummara Madhusudana","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Yong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildoo","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Sik","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang H.","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngmi","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,22]]},"reference":[{"key":"BFncomms10993_CR1","doi-asserted-by":"publisher","first-page":"3058","DOI":"10.1002\/cncr.28843","volume":"120","author":"Y Kim","year":"2014","unstructured":"Kim, Y. et al. 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