Abstract. nasopharyngeal carcinoma (npc) is posing a serious health problem worldwide. the association between its pathogenesis and micrornAs (mirnA) has not been elucidated. In this study, miRNA expression profiling was performed to screen the mirnA expression changes in 8 npc tissues and 4 normal nasopharyngeal tissues. thirtyfour miRNAs were identified to be differentially expressed; of these, one mirnA (miR-18a) was overexpressed and 33 mirnAs (miR-34b, miR-34c, let-7 family, etc.) were underexpressed in npc tissues compared to the normal samples. Validation was performed by real-time quantitative pcr for two altered mirnAs (miR-34b and let-7g) and one nondifferentially expressed mirnA (miR-30c). Unsupervised hierarchical clustering analysis showed that the aberrant mirnAs were correlated with the clinical stage of npc patients. In addition to several biological pathways that are well characterised in npc and which were significantly targeted by the underexpressed mirnAs, two novel pathways, nervous system development and sensory perception of sound, were identified to be strongly associated with NPC development. Furthermore, a c-Myc centered mirnA regulatory network was inferred in npc. our study reveals that aberrantly expressed mirnAs play important roles in npc tumorigenesis and may serve as potential targets for novel therapeutic strategies in the future.
IntroductionMicroRNAs (miRNAs) are a newly identified class of short (about 19-22 nt), endogenous, non-coding, single-stranded rnA molecules, which are conserved in sequence between distantly related organisms. More and more evidence has proved mirnAs play important roles in diverse biological functions, including development, differentiation, proliferation and apoptosis (1,2). MirnAs regulate protein expression by binding to the 3' untranslated regions (3' Utr) of messenger rnAs (mrnAs) and suppressing translation or inducing degradation or deadenylation with varying degrees of sequence complementarity (3). In humans, strong links between cancer and mirnA deregulation have been suggested by recent studies. The relevance of miRNAs to cancer was first reported in 2002 when calin et al observed that miR-15a and miR-16-1 were down-regulated or even deleted in the majority of chronic lymphocytic leukemia patients (4). they also found that many known mirnAs are located in the regions of human chromosomes with high frequencies of copy number alterations in cancers (4). so far, distinct mirnA profiles have been reported and the potential role of mirnAs in various human haematological and solid cancers have been indicated by many studies. lu et al used mirnA expressions to classify human cancers associated with the developmental lineage and differentiation state (5). Johnson et al reported that the down-regulation of let-7 is a significant cause of lung cancer tumorigenesis (6). this body of evidence indicates that the aberrations of mirnA expression in cancer are strongly correlated with tumor carcinogenesis and progression.nasopharyngeal carcinoma (npc) is ...