Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignant cancer prevalent in Southern China and South-eastern Asia. In this study, we aim to elucidate the fundamental role of aberrant expressed microRNAs (miRNA) in NPC tumorigenesis. By comparison of miRNA expression profiles in NPC tumor lines with non-malignant nasopharyngeal epithelial cell, 119 differentially expressed miRNAs were identified in EBV-associated NPC. Among the 58 microRNAs downregulated in NPC, transcriptional silencing of miR-31 was consistently found in both NPC tumor lines and primary tumors. Expression of miR-31 was detected in none of 6 EBV-positive tumor lines and 38 microdissected primary tumors, but in all normal nasopharyngeal epithelia. Interestingly, miR-31 is located at 0.5 Mb telomeric to CDKN2A at 9p21.3, which is commonly homozygous deleted in NPC. Homozygous deletion of both miR-31 and CDKN2A locus was confirmed in 2 tumor lines. In the 4 tumor lines with intact miR-31, hypermethylation of 5′CpG islands was detected by bisulfate sequencing and MSP analysis. Re-expression of miR-31 was demonstrated in the EBV-positive NPC cell line C666-1 treated with 5-aza-2′-deoxycytidine. The findings suggested that homozygous deletion and promoter methylation are the major mechanisms for transcriptional silencing of miR-31 in NPC. By microarray and bioinformatic analysis, we have identified a number of putative targets of miR-31. Among these candidates, we have proven that miR-31 targeted FIH1 and MCM2 expression in NPC. Ectopic expression of miR-31 in NPC cells resulted in repression of FIH1 and MCM2 protein. Finally, we have demonstrated that restoration of miR-31 or knockdown of FIH1 expression significantly suppressed cell proliferation of C666-1. Our findings indicated that miR-31 is a NPC-associated microRNA which negatively regulates cell growth by repressing FIH1 expression.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2288. doi:1538-7445.AM2012-2288</jats:p>