Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer

Metastasis is a multistep molecular network process, which is the major cause of death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. Increased expression of fucosyltransferase4 (FUT4) has been reported to be associated with the invasive and metastatic properties of CRC. Here to identify potential key miRNAs and their target genes for colorectal cancer (CRC), we compared miRNA expression profiles between metastatic CRC cell SW620 and primary CRC cell SW480. Microarray analysis revealed that there were 85 differentially expressed miRNAs in SW620 cells with highly metastatic potential compared to SW480 cells with lowly metastatic potential. The expression of miR-26a and miR-26b were lower in SW620 cells than in SW480 cells, as well as downregulated in tumor tissues than in adjacent normal tissues of CRC patients. By applying bioinformatic approaches for the prediction of miRNA targeting 3'-UTR of FUT4, we identified FUT4 as one of the miR-26a/26b-targeted genes, while the expression of the target gene exhibited patterns opposite to that of miR-26a/26b in CRC cell lines, tumor tissues and corresponding adjacent tissues. Forced miR-26a/26b expression affected migratory behavior of CRC cells and FUT4 expression, while altered expression of FUT4 in CRC cell lines modulated progression upon transfection with miR-26a/26b mimic or inhibiter. FUT4 also regulated directly aggressiveness of SW620 and SW480 cells. Moreover, statistical analyses revealed that low miR-26a/26b levels and high expression of FUT4 were positively correlated with poor overall survival. The identified CRC-restricted miR-26a and miR-26b might be implicated in cancer progression via their target gene FUT4, suggesting their potential usage in CRC treatment.