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dc.contributor.authorWang, Chun-, Ien_US
dc.contributor.authorKao, Huang-Kaien_US
dc.contributor.authorChen, Ting-Wenen_US
dc.contributor.authorHuang, Yenlinen_US
dc.contributor.authorCheng, Hsing-Wenen_US
dc.contributor.authorYi, Jui-Shanen_US
dc.contributor.authorHung, Shag-Yuen_US
dc.contributor.authorWu, Chi-Shengen_US
dc.contributor.authorLee, Yun-Shienen_US
dc.contributor.authorChang, Kai-Pingen_US
dc.date.accessioned2019-08-02T02:15:34Z-
dc.date.available2019-08-02T02:15:34Z-
dc.date.issued1970-01-01en_US
dc.identifier.issn1083-7159en_US
dc.identifier.urihttp://dx.doi.org/10.1634/theoncologist.2019-0063en_US
dc.identifier.urihttp://hdl.handle.net/11536/152245-
dc.description.abstractBackground DNA copy number variations (CNVs) are a hallmark of cancer, and the current study aimed to demonstrate the profile of the CNVs for oral cavity squamous cell carcinoma (OSCC) and elucidate the clinicopathological associations and molecular mechanisms of a potential marker derived from CNVs, mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), in OSCC carcinogenesis. Materials and Methods CNVs in 37 OSCC tissue specimens were analyzed using a high-resolution microarray, the OncoScan array. Gene expression was analyzed by real-time polymerase chain reaction in 127 OSCC and normal tissue samples. Cell function assays included cell cycle, migration, invasion and chromatin immunoprecipitation assays. Results We found a novel copy number amplified region, chromosome 9p, encompassing MLLT3 via the comparison of our data set with six other OSCC genome-wide CNV data sets. MLLT3 overexpression was associated with poorer overall survival in patients with OSCC (p = .048). MLLT3 knockdown reduced cell migration and invasion. The reduced invasion ability in MLLT3-knockdown cells was rescued with double knockdown of MLLT3 and CBP/p300-interacting transactivator with ED rich carboxy-terminal domain 4 (CITED4; 21.0% vs. 61.5%). Knockdown of MLLT3 impaired disruptor of telomeric silencing-1-like (Dot1L)-associated hypermethylation in the promoter of the tumor suppressor, CITED4 (p < .001), and hence dysregulated HIF-1 alpha-mediated genes (TWIST, MMP1, MMP2, VIM, and CDH1) in OSCC cells. Conclusion We identified unique CNVs in tumors of Taiwanese patients with OSCC. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1 alpha-mediated genes. Implications for Practice This article reports unique copy number variations in oral cavity squamous cell carcinoma (OSCC) tumors of Taiwanese patients. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1 alpha-mediated genes.en_US
dc.language.isoen_USen_US
dc.subjectCopy number variationsen_US
dc.subjectOral cavity squamous cell carcinomaen_US
dc.subjectMLLT3en_US
dc.subjectCITED4en_US
dc.subjectHIF-1 alphaen_US
dc.titleCharacterization of Copy Number Variations in Oral Cavity Squamous Cell Carcinoma Reveals a Novel Role for MLLT3 in Cell Invasivenessen_US
dc.typeArticleen_US
dc.identifier.doi10.1634/theoncologist.2019-0063en_US
dc.identifier.journalONCOLOGISTen_US
dc.citation.spage0en_US
dc.citation.epage0en_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.department生物資訊及系統生物研究所zh_TW
dc.contributor.departmentNational Chiao Tung Universityen_US
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.identifier.wosnumberWOS:000474075400001en_US
dc.citation.woscount0en_US
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