microRNAs in tumor progression are crucial in head & neck cancer. Our research group found that miR-450a were significantly higher in 46 clinical OSCC specimens than those in corresponding adjacent non-cancerous specimens (p<0.001). However, its role in oral carcinoma has not been elucidated yet. miR-450a is highly conserved among mammals. In homo sapiens, duplicated miR-450a were located at adjacent loci in X chromosome. Gene expression microarray was performed to identify potential miR-450a mediating genes. Differential gene expressions in pre-miR-450a-transfected DOK and SCC15 were analyzed. Using Gene Set Enrichment Analysis, 16878 & 17000 down-regulated genes were clarified in DOK & SCC15, respectively. To narrow down these miR-450a targeting genes, two gene lists were independently overlapped with target predicted program microRNA.org. These two gene lists were further reduced to 419 genes in DOK & 465 genes in SCC15, and 256 genes were common in both two gene sets. We used RT-PCR to validate a suspected membrane protein, TMEM182. The expression of TMEM182 was down-regulated in RNA and protein levels. We verified that this TMEM182 down-regulation was under a post-translational level mediated by miR-450a. Up-regulation of miR-450a in OSCC would enhance cell detachment ability. But, the cell proliferation was higher in miR-450a overexpressed cells. We suggested that miR-450a regulates cell adhesion through down-regulation of TMEM182, and further influences cell migration in oral cancer.
Date:
2015-04
Relation:
FASEB Journal. 2015 Apr;29(1, Suppl.):Abstract number 711.22.