Abstract
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.
Highlights
As one of the most common malignant cancers worldwide, colorectal cancer (CRC) has become the fifth leading cause of cancer death for men and women in China.[1]
FUT4 is well-known to play an important role in cancer progression, the underlying mechanisms of fucosylation mediated by miRNA remain unknown in CRC
MiRNA expression profile in SW620 and SW480 cells. To test whether these epigenetic differences are associated with changes in the level of miRNA expression and to investigate the role of miRNA in the development of metastasis, we analyzed the miRNA expression profiles of SW620 cells with highly metastatic potential and SW480 cells with lowly metastatic potential
Summary
As one of the most common malignant cancers worldwide, colorectal cancer (CRC) has become the fifth leading cause of cancer death for men and women in China.[1]. FUT4 was highly expressed in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcer.[18] FUT4 was a novel regulator of epithelial–mesenchymal transition (EMT), which was a crucial step in tumor progression in breast cancer cells.[19] FUT4 was overexpressed in most of metastatic colorectal cancer patients and associated with poorer outcomes.[20] In our previous studies, the altered level of Received 17.3.17; accepted 18.5.17; Edited by G Calin miR-26a and miR-26b mediates CRC aggressiveness by targeting FUT4 Y Li et al FUT4 was responsible for changed drug-resistant phenotypes of human hepatocellular carcinoma (HCC) cell lines BEL7402 and BEL/FU cells both in vitro and in vivo.[21] FUT4 is well-known to play an important role in cancer progression, the underlying mechanisms of fucosylation mediated by miRNA remain unknown in CRC
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