Methylation-induced loss of miR-484 in microsatellite-unstable colorectal cancer promotes both viability and IL-8 production via CD137L
Methylation-induced loss of miR-484 in microsatellite-unstable colorectal cancer promotes both viability and IL-8 production via CD137L
复制标题
微卫星不稳定结直肠癌中甲基化诱导的 miR-484 丢失可通过 CD137L 促进活力和 IL-8 产生。
DOI：
10.1002/path.4525
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发表时间：
2015-06-01
影响因子：
7.3
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Mei, Qian;Xue, Geng;Han, Weidong
表现为微卫星不稳定性的结直肠癌(CRC)是一种定义明确的亚型，具有错配修复途径缺陷和典型的临床病理特征。我们的目标是确定完整的miRNome及其在MSI CRC中的分子病理作用。我们分析了miRNA在MSI CRC中的表达，并将其与MSS对应的表达进行了比较。微阵列和qRT-PCR分析鉴定出8个能够区分癌组织MSI状态的miRNAs。在MSI CRC中，miR-484是最显著降低的miRNA，主要由CpG岛甲基化表型介导。MIR-484作为肿瘤抑制因子在体外和体内都能抑制MSI CRC细胞的活性。此外，miR-484抑制CD137L的表达，从而抑制MSI CRC细胞产生IL-8。我们的研究结果有助于更好地理解异常的miRNAs在MSI CRCs不同表型特征中的作用，并为这些患者的早期诊断和基因治疗提供了一种选择。版权所有(C)2015年大不列颠和爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
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 (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.