Methylation‐induced loss of miR ‐484 in microsatellite‐unstable colorectal cancer promotes both viability and IL ‐8 production via CD137L

Colorectal cancer ( CRC ) exhibiting MSI (microsatellite instability) represents a well‐defined subtype characterized by a deficient mismatch repair pathway and typical clinico‐pathological features. Our objective was to identify the entire miRNome and its molecular pathological roles in MSI CRCs . We profiled miRNA expression in MSI CRCs and compared it with MSS counterparts. Microarray and qRT‐PCR analysis identified eight miRNAs that could distinguish the MSI status of CRCs . MiR ‐484 was the most significantly decreased miRNA in MSI CRCs , primarily mediated by the CpG island methylator phenotype. MiR ‐484 functions as a tumour suppressor to inhibit MSI CRC cell viability in vitro and in vivo . Moreover, miR ‐484 repressed CD137L expression and thereby attenuated IL ‐8 production by MSI CRC cells. Our results contribute to a better understanding of the roles of dysregulated miRNAs in the distinct phenotypic features of MSI CRCs and indicate an option for early diagnosis and gene therapy for these patients. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.