The role of the miR-200 family in epithelial-mesenchymal transition.

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Genes encoding miRNAs are located in regions of the genome that are commonly amplified, deleted or rearranged. They are commonly dysregulated in human cancers and known to act as oncogenes or tumor suppressors. Members of the miR-200 miRNA family are downregulated in human cancer cells and tumors due to aberrant epigenetic gene silencing and play a critical role in the suppression of epithelial-to-mesenchymal transition (EMT), tumor cell adhesion, migration, invasion and metastasis, by targeting and repressing the expression of key mRNAs that are involved in EMT (ZEB1 and ZEB2), β-catenin/Wnt signaling (β-catenin), EGFR inhibitor resistance (ERRFI-1) and chemoresistance to therapeutic agents (TUBB3). Since the miR-200 family functions as putative tumor suppressors and represent biomarkers for poorly differentiated and aggressive cancers, restoration of miR-200 expression may have therapeutic implications for the treatment of metastatic and drug-resistant tumors.