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dc.contributor.authorChan, Chieh-Hsiangen_US
dc.contributor.authorChen, Chun-Mingen_US
dc.contributor.authorLee, Yan-Hwa Wuen_US
dc.contributor.authorYou, Li-Ruen_US
dc.date.accessioned2019-04-02T06:00:34Z-
dc.date.available2019-04-02T06:00:34Z-
dc.date.issued2019-02-01en_US
dc.identifier.issn1541-7786en_US
dc.identifier.urihttp://dx.doi.org/10.1158/1541-7786.MCR-18-0551en_US
dc.identifier.urihttp://hdl.handle.net/11536/148803-
dc.description.abstractThe pleiotropic roles of DEAD-box helicase 3, X-linked (DDX3X), including its functions in transcriptional and translational regulation, chromosome segregation, DNA damage, and cell growth control, have highlighted the association between DDX3X and tumorigenesis. However, mRNA transcripts and protein levels of DDX3X in patient specimens have shown the controversial correlations of DDX3X with hepatocellular carcinoma (HCC) prevalence. In this study, generation of hepatocyte-specific Ddx3x-knockout mice revealed that loss of Ddx3x facilitates liver tumorigenesis. Loss of Ddx3x led to profound ductular reactions, cell apoptosis, and compensatory proliferation in female mutants at 6 weeks of age. The sustained phosphorylation of histone H2AX (gamma H2AX) and significant accumulation of DNA single-strand breaks and double-strand breaks in liver indicated that the replicative stress occurred in female mutants. Further chromatin immunoprecipitation analyses demonstrated that DDX3X bound to promoter regions and regulated the expression of DNA repair factors, DDB2 and XPA, to maintain genome stability. Loss of Ddx3x led to decreased levels of DNA repair factors, which contributed to an accumulation of unrepaired DNA damage, replication stress, and eventually, spontaneous liver tumors and DEN-induced HCCs in Alb-Cre/+Ddx3xflox/flox mice. Implications: These data identify an important role of DDX3X in the regulation of DNA damage repair to protect against replication stress in liver and HCC development and progression.en_US
dc.language.isoen_USen_US
dc.titleDNA Damage, Liver Injury, and Tumorigenesis: Consequences of DDX3X Lossen_US
dc.typeArticleen_US
dc.identifier.doi10.1158/1541-7786.MCR-18-0551en_US
dc.identifier.journalMOLECULAR CANCER RESEARCHen_US
dc.citation.volume17en_US
dc.citation.spage555en_US
dc.citation.epage566en_US
dc.contributor.department交大名義發表zh_TW
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentNational Chiao Tung Universityen_US
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000457397800020en_US
dc.citation.woscount0en_US
Appears in Collections:Articles