Distinct methylation levels of mature microRNAs in gastrointestinal cancers
Distinct methylation levels of mature microRNAs in gastrointestinal cancers
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DOI：
10.1038/s41467-019-11826-1
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发表时间：
2019-08-29
影响因子：
16.6
通讯作者：
Ishii, Hideshi
中科院分区：
文献类型：
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作者：
Konno, Masamitsu;Koseki, Jun;Ishii, Hideshi
传统上，基于miRNA以不变的方式识别和调节其靶标的假设，根据它们的RNA表达水平来评估微（mi）RNA的生物学意义。在这里，我们发现一部分成熟的miRNAs，包括miR-17- 5 p，-21-5p和-200c-3p和let-7a-5 p，含有甲基标记，可能会改变它们的稳定性和靶点识别。重要的是，与配对的正常组织相比，这些miRNA的甲基化在癌组织中显著增加。此外，血清样本中的miR-17- 5 p甲基化水平以极高的灵敏度和特异性区分早期胰腺癌患者和健康对照。这些发现为早期癌症的诊断策略提供了基础，并为我们对miRNA生物学的理解增加了一个维度。
The biological significance of micro (mi)RNAs has traditionally been evaluated according to their RNA expression levels based on the assumption that miRNAs recognize and regulate their targets in an unvarying fashion. Here we show that a fraction of mature miRNAs including miR-17-5p, -21-5p, and -200c-3p and let-7a-5p harbor methyl marks that potentially alter their stability and target recognition. Importantly, methylation of these miRNAs was significantly increased in cancer tissues as compared to paired normal tissues. Furthermore, miR-17-5p methylation level in serum samples distinguished early pancreatic cancer patients from healthy controls with extremely high sensitivity and specificity. These findings provide a basis for diagnostic strategies for early-stage cancer and add a dimension to our understanding of miRNA biology.