| Summary: | 博士 === 國立中山大學 === 生物醫學研究所 === 107 === Urinary bladder urothelial carcinoma (UBUC) is a common urologic cancer in urinary system, our studies revealed that the B-cell CLL/lymphoma 6 (BCL6) gene mapped to 3q27 was amplified in muscle-invasive UBUC patients. Knockdown of the BCL6 gene suppressed tumor growth in vivo, supporting its oncogenic roles in vivo. Overexpression of the BCL6 gene in UBUC-derived cells increased cell cycle progression, cell proliferation, tumor anchorage-independent growth, cell migration and cell invasion; suppressed cyclin dependent kinase inhibitors (CKIs) mRNA and protein levels. Knockdown of the BCL6 gene in UBUC-derived cells cycle progression, cell proliferation, tumor anchorage-independent growth, cell migration, cell invasion, and CKIs mRNA and protein levels in opposite results. In microarray results, we found that BCL6 regulated Forkhead box O3 (FOXO3) signaling pathway. BCL6 upregulates cell proliferation by increasing FOXO3 phosphorylation through MAPK1/3 and PI3K pathways, and dwonregulates CDKN1A and CDKN1B mRNA levels. BCL6 suppresses cell apoptosis and inhibition of BCL6 sensitizes cisplatin-resistant cells to cisplatin. The BCL6 may be used as a potential biomarker or therapeutic target for UBUC patients.
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