Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Cancer Profiling Discovery/ Medical Data Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Nat Commun. 2019 Aug 29;10(1):3888. doi: 10.1038/s41467-019-11826-1.
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.
miRNAs 的生物学意义传统上是根据它们的 RNA 表达水平来评估的，这是基于 miRNA 以不变的方式识别和调节其靶标这一假设。在这里，我们发现一部分成熟的 miRNAs 包括 miR-17-5p、-21-5p、-200c-3p 和 let-7a-5p 具有甲基化标记，这些标记可能改变它们的稳定性和靶标识别。重要的是，与配对的正常组织相比，这些 miRNAs 在癌症组织中的甲基化水平显著增加。此外，血清样本中 miR-17-5p 的甲基化水平可以区分早期胰腺癌患者和健康对照者，具有极高的灵敏度和特异性。这些发现为早期癌症的诊断策略提供了依据，并为我们理解 miRNA 生物学增加了一个维度。
