Abstract

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.

Details

Title
Distinct methylation levels of mature microRNAs in gastrointestinal cancers
Author
Konno, Masamitsu 1   VIAFID ORCID Logo  ; Koseki, Jun 2 ; Asai, Ayumu 3 ; Yamagata, Akira 4 ; Shimamura, Teppei 5 ; Motooka, Daisuke 6 ; Okuzaki, Daisuke 6   VIAFID ORCID Logo  ; Kawamoto, Koichi 7 ; Mizushima, Tsunekazu 7 ; Eguchi, Hidetoshi 7 ; Takiguchi, Shuji 8 ; Satoh, Taroh 1 ; Mimori, Koshi 9 ; Ochiya, Takahiro 10 ; Doki, Yuichiro 7 ; Ofusa, Ken 4 ; Mori, Masaki 7 ; Ishii, Hideshi 2 

1  Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 
2  Department of Cancer Profiling Discovery/ Medical Data Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 
3  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 
4  Prophoenix Division, Food and Life-Science Laboratory, Idea Consultants, Inc., Osaka-city, Osaka, Japan 
5  Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan 
6  Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan 
7  Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 
8  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 
9  Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan 
10  Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan 
Pages
1-7
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11826-1
ProQuest document ID
2282442161
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.