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dc.contributor.authorLi, Hao-Kangen_US
dc.contributor.authorMai, Ru-Tsunen_US
dc.contributor.authorHuang, Hsien-Daen_US
dc.contributor.authorChou, Chih-Hungen_US
dc.contributor.authorChang, Yi-Anen_US
dc.contributor.authorChang, Yao-Wenen_US
dc.contributor.authorYou, Li-Ruen_US
dc.contributor.authorChen, Chun-Mingen_US
dc.contributor.authorLee, Yan-Hwa Wuen_US
dc.date.accessioned2019-04-03T06:42:03Z-
dc.date.available2019-04-03T06:42:03Z-
dc.date.issued2016-06-27en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://dx.doi.org/10.1038/srep28637en_US
dc.identifier.urihttp://hdl.handle.net/11536/133918-
dc.description.abstractStudies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion, and most importantly, DDX3 knockdown promotes tumorigenesis. Moreover, we found positive correlations between DDX3 level and expressions of tumor-suppressive miR-200b, miR-200c, miR-122 and miR-145, but not miR-10b and miR-519a, implying their involvement in DDX3 knockdown-induced CSC phenotypes. In addition, DDX3 reduction promoted up-regulation of DNA methyltransferase 3A (DNMT3A), while neither DNMT3B nor DNMT1 expression was affected. Enriched DNMT3A binding along with hypermethylation on promoters of these tumor-suppressive miRNAs reflected their transcriptional repressions in DDX3-knockdown cells. Furthermore, individual restoration of these tumor-suppressive miRNAs represses DDX3 knockdown-induced CSC phenotypes. In conclusion, our study suggested that DDX3 prevents generation of CSCs through epigenetically regulating a subset of tumor-suppressive miRNAs expressions, which strengthens tumor suppressor role of DDX3 in HCC.en_US
dc.language.isoen_USen_US
dc.titleDDX3 Represses Stemness by Epigenetically Modulating Tumor-suppressive miRNAs in Hepatocellular Carcinomaen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/srep28637en_US
dc.identifier.journalSCIENTIFIC REPORTSen_US
dc.citation.volume6en_US
dc.citation.spage0en_US
dc.citation.epage0en_US
dc.contributor.department生物科技學院zh_TW
dc.contributor.department生醫工程研究所zh_TW
dc.contributor.departmentCollege of Biological Science and Technologyen_US
dc.contributor.departmentInstitute of Biomedical Engineeringen_US
dc.identifier.wosnumberWOS:000378515400002en_US
dc.citation.woscount11en_US
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