Distinct methylation levels of mature microRNAs in gastrointestinal cancers

Masamitsu Konno, Jun Koseki, Ayumu Asai, Akira Yamagata, Teppei Shimamura, Daisuke Motooka, Daisuke Okuzaki, Koichi Kawamoto, Tsunekazu Mizushima, Hidetoshi Eguchi, Shuji Takiguchi, Taroh Satoh, Koshi Mimori, Takahiro Ochiya, Yuichiro Doki, Ken Ofusa, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3888
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

methylation
Gastrointestinal Neoplasms
Methylation
MicroRNAs
cancer
target recognition
harbors
biology
serums
Tissue
Ports and harbors
Pancreatic Neoplasms
sensitivity
Neoplasms
RNA
Sensitivity and Specificity
Serum

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Konno, M., Koseki, J., Asai, A., Yamagata, A., Shimamura, T., Motooka, D., ... Ishii, H. (2019). Distinct methylation levels of mature microRNAs in gastrointestinal cancers. Nature communications, 10(1), [3888]. https://doi.org/10.1038/s41467-019-11826-1

Distinct methylation levels of mature microRNAs in gastrointestinal cancers. / 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.

In: Nature communications, Vol. 10, No. 1, 3888, 01.12.2019.

Research output: Contribution to journalArticle

Konno, M, Koseki, J, Asai, A, Yamagata, A, Shimamura, T, Motooka, D, Okuzaki, D, Kawamoto, K, Mizushima, T, Eguchi, H, Takiguchi, S, Satoh, T, Mimori, K, Ochiya, T, Doki, Y, Ofusa, K, Mori, M & Ishii, H 2019, 'Distinct methylation levels of mature microRNAs in gastrointestinal cancers', Nature communications, vol. 10, no. 1, 3888. https://doi.org/10.1038/s41467-019-11826-1
Konno M, Koseki J, Asai A, Yamagata A, Shimamura T, Motooka D et al. Distinct methylation levels of mature microRNAs in gastrointestinal cancers. Nature communications. 2019 Dec 1;10(1). 3888. https://doi.org/10.1038/s41467-019-11826-1
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. / Distinct methylation levels of mature microRNAs in gastrointestinal cancers. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{abfc51fb27764a33b6d2904cd30414b0,
title = "Distinct methylation levels of mature microRNAs in gastrointestinal cancers",
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.",
author = "Masamitsu Konno and Jun Koseki and Ayumu Asai and Akira Yamagata and Teppei Shimamura and Daisuke Motooka and Daisuke Okuzaki and Koichi Kawamoto and Tsunekazu Mizushima and Hidetoshi Eguchi and Shuji Takiguchi and Taroh Satoh and Koshi Mimori and Takahiro Ochiya and Yuichiro Doki and Ken Ofusa and Masaki Mori and Hideshi Ishii",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-11826-1",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Distinct methylation levels of mature microRNAs in gastrointestinal cancers

AU - Konno, Masamitsu

AU - Koseki, Jun

AU - Asai, Ayumu

AU - Yamagata, Akira

AU - Shimamura, Teppei

AU - Motooka, Daisuke

AU - Okuzaki, Daisuke

AU - Kawamoto, Koichi

AU - Mizushima, Tsunekazu

AU - Eguchi, Hidetoshi

AU - Takiguchi, Shuji

AU - Satoh, Taroh

AU - Mimori, Koshi

AU - Ochiya, Takahiro

AU - Doki, Yuichiro

AU - Ofusa, Ken

AU - Mori, Masaki

AU - Ishii, Hideshi

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071627062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071627062&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-11826-1

DO - 10.1038/s41467-019-11826-1

M3 - Article

C2 - 31467274

AN - SCOPUS:85071627062

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3888

ER -