Distinct methylation levels of mature microRNAs in gastrointestinal cancers.,Nature Communications

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Distinct methylation levels of mature microRNAs in gastrointestinal cancers.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-29 , DOI: 10.1038/s41467-019-11826-1
Masamitsu Konno ₁ , Jun Koseki ₂ , Ayumu Asai _{1,

2} , Akira Yamagata ₃ , Teppei Shimamura ₄ , Daisuke Motooka ₅ , Daisuke Okuzaki ₅ , Koichi Kawamoto ₆ , Tsunekazu Mizushima ₆ , Hidetoshi Eguchi ₆ , Shuji Takiguchi _{6,

7} , Taroh Satoh ₁ , Koshi Mimori ₈ , Takahiro Ochiya ₉ , Yuichiro Doki ₆ , Ken Ofusa ₃ , Masaki Mori ₆ , Hideshi Ishii ₂

Affiliation

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.
Prophoenix Division, Food and Life-Science Laboratory, Idea Consultants, Inc., Osaka-city, Osaka, Japan.
Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Aichi, Japan.
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.

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.

中文翻译：

胃肠道癌症中成熟microRNA的不同甲基化水平。

传统上，基于miRNA的识别水平是基于miRNA识别并调节其靶标的假设，根据其RNA表达水平评估其生物学意义。在这里，我们显示了一部分成熟的miRNA，包括miR-17-5p，-21-5p和-200c-3p和let-7a-5p带有甲基标记，这些甲基标记可能会改变其稳定性和靶标识别能力。重要的是，与配对的正常组织相比，这些miRNA的甲基化在癌症组织中显着增加。此外，血清样品中的miR-17-5p甲基化水平以极高的敏感性和特异性将早期胰腺癌患者与健康对照区分开。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生物学的理解增添了新的内容。

更新日期：2019-08-29

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