The microRNAs miR-373 and miR-520c promote tumor migration, invasion and metastasis

MicroRNAs (miRNAs) are single-stranded noncoding RNAs that play important roles in many biological processes. Although the oncogenic and tumor suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumor metastasis was only recently addressed and still remain largely unexplored. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic human breast tumor cell line that was transduced with a miRNA expression library and subjected to a trans-well migration assay. We found human miR-373 and 520c to stimulate cancer cell migration as well as tumor cell invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by their suppression of CD44 expression. Finally, we found significant up-regulation of miR-373 expression in clinical breast cancer primary and metastasis samples that inversely correlated with CD44 expression. Taken together, our study indicates that miRNAs are involved in tumor migration and invasion and implicates miR-373 and conceivably miR-520c as metastasis-promoting miRNAs. Keywords: human breast cancer cell MCF7 vs MCF7 expressing miR-373 vs MCF7 expressing miR-520c