Distinct methylation levels of mature microRNAs in gastrointestinal cancers

被引:144
作者
Konno, Masamitsu [1 ]
Koseki, Jun [2 ]
Asai, Ayumu [1 ,2 ]
Yamagata, Akira [3 ]
Shimamura, Teppei [4 ]
Motooka, Daisuke [5 ]
Okuzaki, Daisuke [5 ]
Kawamoto, Koichi [6 ]
Mizushima, Tsunekazu [6 ]
Eguchi, Hidetoshi [6 ]
Takiguchi, Shuji [6 ,7 ,8 ]
Satoh, Taroh [1 ]
Mimori, Koshi [9 ]
Ochiya, Takahiro [10 ]
Doki, Yuichiro [6 ]
Ofusa, Ken [3 ]
Mori, Masaki [6 ]
Ishii, Hideshi [2 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, Suita, Osaka, Japan
[2] Osaka Univ, Grad Sch Med, Dept Canc Profiling Discovery Med Data Sci, Suita, Osaka, Japan
[3] Idea Consultants Inc, Food & Life Sci Lab, Prophoenix Div, Osaka, Osaka, Japan
[4] Nagoya Univ, Div Syst Biol, Grad Sch Med, Nagoya, Aichi, Japan
[5] Osaka Univ, Genome Informat Res Ctr, Res Inst Microbial Dis, Osaka, Japan
[6] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Suita, Osaka, Japan
[7] Nagoya City Univ, Dept Gastroenterol Surg, Grad Sch Med Sci, Nagoya, Aichi, Japan
[8] Med Sch, Nagoya, Aichi, Japan
[9] Kyushu Univ, Dept Surg, Beppu Hosp, Beppu, Oita, Japan
[10] Natl Canc Ctr, Div Mol & Cellular Med, Res Inst, Tokyo, Japan
关键词
MASS-SPECTROMETRY; TRANSFER-RNA; N-6-METHYLADENOSINE;
D O I
10.1038/s41467-019-11826-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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收藏
页数:7
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