Distinct methylation levels of mature microRNAs in gastrointestinal cancers

• Published in: Nature communications Vol. 10; no. 1; pp. 3888 - 7
• Main Authors: Konno, Masamitsu, Koseki, Jun, Asai, Ayumu, Yamagata, Akira, Shimamura, Teppei, Motooka, Daisuke, Okuzaki, Daisuke, Kawamoto, Koichi, Mizushima, Tsunekazu, Eguchi, Hidetoshi, Takiguchi, Shuji, Satoh, Taroh, Mimori, Koshi, Ochiya, Takahiro, Doki, Yuichiro, Ofusa, Ken, Mori, Masaki, Ishii, Hideshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.08.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/91; 631/208/68/2486; 631/67/1857; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cancer; Cell Line, Tumor; Diagnostic systems; Epigenomics; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Methylation; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular Dynamics Simulation; multidisciplinary; Pancreatic cancer; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Target recognition
• ISSN: 2041-1723; 2041-1723
• 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. In cancer it is assumed that microRNAs recognise and regulate their targets uniformly. Here, the authors show that in gastrointestinal cancers methylation of microRNAs may impact their stability, and that levels of microRNA methylation are distinct in pancreatic cancer patients compared to healthy controls with potential diagnostic implications.