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Methylation‐induced loss of miR ‐484 in microsatellite‐unstable colorectal cancer promotes both viability and IL ‐8 production via CD137L
Author(s) -
Mei Qian,
Xue Geng,
Li Xiang,
Wu Zhiqiang,
Li Xiaolei,
Yan Hongli,
Guo Mingzhou,
Sun Shuhan,
Han Weidong
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4525
Subject(s) - microsatellite instability , microrna , cancer research , colorectal cancer , biology , methylation , phenotype , cpg site , microarray , cancer , dna mismatch repair , dna methylation , gene , microsatellite , gene expression , genetics , allele
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.