| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 98 === Abstract
Previously, we reported that EBV oncoprotein latent membrane protein 1 (LMP1) activates DNA methyltransferase 1 (DNMT1), which induces DNA hypermethylation and causes gene silencing in nasopharyngeal carcinoma (NPC). Aberrant DNA methylation is considered one of the major causes that lead to gene inactivation; hence, hypermethylation of tumor suppressor genes (TSGs) may promote cancer formation. Here, we identified a differential methylated gene, POU3F1, a transcription factor regulating keratinocyte differentiation and neurogenesis, in NPC tumor. Bisulfite sequencing results indicated that POU3F1 methylation percentage was relatively higher in NPC tumor when compared with adjacent normal tissues. The results were consistent with quantitative RT-PCR results where POU3F1 mRNA expression level was relatively low in NPC. Addition of 5’Aza-dC, a DNA methylation inhibitor, restored mRNA expression in NPC cells suggesting POU3F1 promoter activity could be regulated by DNA methylation. We further analyzed the regulation of POU3F1 promoter by Luc-reporter assay. There are four potential p300/CBP binding sites located at proximal POU3F1 promoter; over-expression of p300/CBP induced POU3F1 promoter activity in vitro. Preliminary functional study indicated that POU3F1 may reduce NPC cell proliferation rate. Its biological function in NPC will be discussed.
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