Identification of Hypermethylated Microrna Genes in NPC

Nasopharyngeal carcinoma (NPC) is a malignant tumor originated from squamous epithelium. Numerous genetic aberrations have been detected in NPC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Inactivation of TSGs by DNA methylation, has become an important mechanism in tumorigenesis. Our previous work indicated that DNA methyltransferase (DNMT) expression is elevated in NPC tumor when compared with adjacent non-tumor suggesting DNA hypermethylation may be critical in NPC pathogenesis. In cancer cells, aberrant DNAmethylation in promoter region often correlates with the inactivation or silencing of the TSG. Hence, gene targets of DNMT may be considered as TSG candidates. Besides coding cellular genes, the expression of non-coding microRNA (miR) genes can also be repressed by DNAmethylation. As each miRs is a negative translational regulator of 800~1000 cellular mRNAs, aberrant deregulation of TSG-miRs (miRs that negatively regulate oncogenes) due to DNAmethylation may lead to promotion of cancerous phenotype. Taken together, the specific aims of this proposal are (1) to identify and validate the methylation status of potential hypermethylated genes including tumor suppressor genes and miRs in NPC cell lines; (2) to identify the gene targets of hypermethylated miRs in NPC cells; (3) to examine the biological functions of these hypermethylated miR genes and miR downstream gene targets, and their roles in NPC tumorigenesis.

Project ID:PA10007-0795
External Project ID:NSC100-2311-B182-004