Regulatory mechanism and target genes of miR-34c in nasopharyngeal carcinoma
Autor: | Jhong Syuan Liu, 劉忠軒 |
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Rok vydání: | 2008 |
Druh dokumentu: | 學位論文 ; thesis |
Popis: | 96 We used Q-RT-PCR to explore microRNA (miRNA) expression level in NPC tissues. Compared with the normal tissues, miR-34c is down-regulated in NPC tumor tissues. In order to study the targets and biological functions, we overexpressed miR-34c in NPC cells and performed microarray to detect differentially expressed genes. Microarray analysis detected 846 genes differentially expressing in NPC cells overexpressing miR-34c. TargetScan and miRBase were used to predict potential miR-34c binding sites on the 3’UTR in these genes. Biological functions of individual genes were extracted from OMIM database. Eight candidates which contained potential miR-34c binding sites and were involved in cell cycle control or tumorgenesis were selected and six candidates were validated with Q-PCR. Previous studies have shown that miR-34s expression is down-regulated when p53 signaling is disrupted. However, p53 pathway is intact in most NPC tumors and cell lines. We identified a CpG island in the promoter region of miR-34b/c and found that the CpG island is hypermethylated in three NPC cell lines. Treatment with 5-aza-2’-deoxycytidine(DAC) restored the expression of miR-34c, suggesting that promoter methylation may provide an additional regulatory mechanism for miR-34s expression. |
Databáze: | Networked Digital Library of Theses & Dissertations |
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