The Role of MicroRNAs in Human Nasopharyngeal Carcinoma

Despite significant improvement in locoregional control in the contemporary era, nasopharyngeal carcinoma (NPC) patients still suffer from a significant risk of distant metastasis (DM). Thus, developing methods to better identify and treat NPC patients at risk of DM is of paramount importance. MicroRNAs (miRNAs) have been shown to provide insight into both the biology and clinical behaviour of human cancers; hence, this thesis aims to characterize both the biological function and the prognostic utility of miRNAs in NPC.First, miR-375 was identified as the most consistently and significantly down-regulated miRNA in head and neck cancer samples (including NPC) analyzed. Functional experiments confirmed a tumour suppressor role for miR-375. A novel target of miR-375, metadherin, was identified as a likely mediator of these effects; possibly through activation of the PI3K/Akt pathway. In addition, a clinical relationship was observed wherein NPC patients whose tumours expressed high metadherin transcript levels had an increased risk of developing distant metastases.Next, a 4-miRNA expression signature associated with risk of DM was identified in a training set of 125 NPC patients (HR 8.25; pPh.D