microRNA expression profiling of nasopharyngeal carcinoma.
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. Thirty-four 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 non-differentially 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.
- SourceAvailable from: Jian Zheng[show abstract] [hide abstract]
ABSTRACT: Nasopharyngeal carcinoma (NPC) is treated with radiotherapy and other modalities, but there is little information on individual genetic factors to help predict and improve patient outcomes. Single nucleotide polymorphisms (SNPs) in mature microRNA (miRNA) sequences have the potential to exert broad impact since miRNAs target many mRNAs. The aim of this study was to evaluate the effects of SNPs in mature miRNA sequences on clinical outcome in NPC patients receiving radiotherapy. In particular, we analyzed associations between seven SNPs and NPC locoregional recurrence (LRR) in 837 patients from eastern China, validating the findings in an additional 828 patients from southern China. We found that miRNA-608 rs4919510C>G exhibited a consistent association with LRR in the discovery set (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.35-3.21), the validation set (HR=2.24; 95%CI=1.45-3.38), and the combined data set (HR=2.08; 95%CI=1.41-3.26). Biochemical investigations demonstrated that rs4919510C>G affects expression of miRNA-608 target genes along with NPC cell growth after irradiation in vivo and in vitro. Notably, X-ray radiation induced more chromatid breaks in lymphocyte cells from rs4919510CC carriers than in those from subjects with other genotypes (P=0.0024). Our findings reveal rs4919510C>G in miRNA-608 as a simple marker to predict locoregional recurrence in radiotherapy-treated NPC patients.Cancer Research 06/2013; · 8.65 Impact Factor