Roles Of MiRNA In Regulating Metastasis Of Colorectal Cancer

[Purpose]MicroRNAs (miRNAs) have emerged relatively as a new class of small,non-coding RNAs that regulate gene expression. To date, more than400miRNAs have been found in diverse animals and plants. MiRNA’s functions have been identified in several aspects, such as cell proliferation, cell death, neuronal patterning, hematopoietic lineage differentiation, cancer pathogenesis, development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, we have uncovered roles for miRNA in the coordination of cancer metastasis.[Experimental Design]The possible interaction between miRNAs and metastasis was investigated using human colon cancer SW480and SW620cell lines. The changes of miRNAs during the metastasis were investigated using miRNA expression array and Northern blot. The target genes were investigated using mRNA expression array combining with bioinformations. And the targets were further conformed by GFP sensor assay. The effect of mRNAs being regulated by miRNAs was investigated using mRNA expression array and RT-PCR. The changes of protein level were examined by Western Blot.[Results]Through miRNA expression array, we found miR-10a was over-expressed in SW480compared with SW620cells, and Northern blot confirmed it. Interestingly, we also found the different expression of miR-10a in colon cancers samples was consistent with that in the SW480and SW620. Using gene microarray method, we compared the gene expression profile discrepancy between SW480with negative control and SW480with miR-10a knocking down. We found three miR-10a’s candidate target metastasis genes combining with bioinformations. One of the candidate targets, ACTG1, was successfully conformed by GFP sensor assay. RT-PCR and Western Blot also confirmed the effect of miR-lOa on ACTG1.TConclusion]To the best of our knowledge, this is the first report demonstrating that miRNAs affect metastasis genes via mediating metastasis genes expression and providing insights of miRNAs may involve cancer metastasis mechanisms.