Panel investigation of microRNAs on the regulation of invasion phenotype in head-neck cancer

• Main Authors: Yu Shan Huang, 黃郁珊
• Other Authors: A. J. Cheng
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/54598975690655360789

碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 101 === Head-neck cancer (HNC) is one of the most common malignancies in the world. The invasion phenotype leading to cancer metastasis is responsible for poor prognosis. To search for microRNA (miRNA) molecules which may associate with cancer invasion, our laboratory has performed miRNA array profiling in three pairs of parental and highly invasion sublines of HNC cells. With the average more than 2-fold change, 24 miRNAs were found considerably differential expression. In which, 17 were up-regulated and 7 down-regulated in the invasion sublines. After analysis by RT-qPCR, 3 miRNAs possessing highest level of differential expression and statistical significance were selected, as miR-548b, miR-622 and miR-638. Functional characterization for each miRNA was performed in two HNC cell lines. Over-expression of miR-548b, miR-622, or miR-638 significantly induced cellular abilities of invasion (2.0 - 14.6 folds) and migration (2.7 - 6.7 folds). Moreover, the promotion of cell mobility by these miRNAs was accompanied with cellular epithelial- mesenchymal transition (EMT), as demonstrated by the alterations of specific EMT markers. The significance of these miRNAs was further supported by preliminary results of clinical association study. Compared to the healthy subjects, these miRNAs were found up-regulations in the plasma of HNC patients, with 3.0-, 3.9- and 14.2-fold of elevations respectively for miR-548b, miR-622 and miR-638 (all P values <0.05). These elevations also possessed the trend in association with advanced cancer stage. In conclusion, we have identified 24 miRNAs significantly associated with invasion phenotypes of HNC, including miR-548b, miR-622 and miR-638 as a panel. This panel miRNA actively participates in cancer formation through promoting cell migration and invasion. Our clinical study suggests that this panel miRNA possess high potential as plasma biomarkers for better management of HNC.