Aberrant Epigenetic Regulation of miRNAs and Dysregulated Signaling Pathways in NPC

MicroRNAs (miRNAs) are noncoding small RNAs with ~22nt. MiRNAs can negatively regulate the translation of 500~800 target mRNAs through the binding between miRNA seed sequence and 3’UTR of target mRNAs. Aberrant cellular miRNA expression is often observed in various cancers and one of the reasons that cause dysregulated miRNA expression is DNA methylation. Nasopharyngeal carcinoma (NPC), a malignant tumor originated from squamous epithelium, is associated with EBV infection. To elucidate whether these aberrantly expressed cellular miRNAs may contribute to the NPC tumorigenesis and may be correlated to DNA methylation, we first performed genome-wide miRNA profiling to identify the differentially expressed miRNAs in NPC cells in the presence or absence of DNA methylation inhibitor 5’aza. Then, we applied web-based miRNA database TargetScan to predict the potential cellular target genes of each dysregulated miRNA. This gene list was further intersected with our previous established cDNA microarray data from the NPC tumor versus adjacent normal tissues. From the intersected gene list, we may correlate the DNA methylation downregulated miRNAs to their overexpressed corresponding cellular mRNA targets in NPC. The specific aims of this proposal are (1) to identify the hypermethylated cellular miRNAs in NPC cells; (2) to understand the mechanism of the miRNA expression dysregulation (3) to validate the target genes of the dysregulated miRNAs in NPC cells; and (4) to examine the biological functions of the dysregulated miRNA targets, their signaling pathways and their roles in NPC tumorigenesis.

Project ID:PC10408-1510
External Project ID:MOST104-2320-B182-033-MY3