5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs

Although 5-methylcytosine (m 5 C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m 5 C modifications in human urothelial carcinoma of the...

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Vydáno v:	Nature cell biology Ročník 21; číslo 8; s. 978 - 990
Hlavní autoři:	Chen, Xin, Li, Ang, Sun, Bao-Fa, Yang, Ying, Han, Ya-Nan, Yuan, Xun, Chen, Ri-Xin, Wei, Wen-Su, Liu, Yanchao, Gao, Chun-Chun, Chen, Yu-Sheng, Zhang, Mengmeng, Ma, Xiao-Dan, Liu, Zhuo-Wei, Luo, Jun-Hang, Lyu, Cong, Wang, Hai-Lin, Ma, Jinbiao, Zhao, Yong-Liang, Zhou, Fang-Jian, Huang, Ying, Xie, Dan, Yang, Yun-Gui
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.08.2019 Nature Publishing Group
Témata:	101/58 42/70 42/89 45/90 45/91 5-Methylcytosine - metabolism 631/337/1645/2020 631/337/1645/2570 631/67 64/60 82/1 82/83 Animals Biomedical and Life Sciences Bladder Bladder cancer Cancer Cancer Research Carcinoma, Transitional Cell - genetics Carcinoma, Transitional Cell - metabolism Cell Biology Cold shock Cytosine Development and progression Developmental Biology Gene Expression Regulation - genetics Genetic aspects Health aspects Humans Indoles Life Sciences Messenger RNA Methylation Methyltransferases - genetics Mice mRNA stability Nucleotides Pathogenesis Physiological aspects RNA, Messenger - genetics Stem Cells Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Urothelial carcinoma Y-Box-Binding Protein 1 - genetics China
ISSN:	1465-7392, 1476-4679, 1476-4679
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Shrnutí:	Although 5-methylcytosine (m 5 C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m 5 C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m 5 C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m 5 C ‘reader’ recognizing m 5 C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m 5 C methylation site in the HDGF 3′ untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m 5 C-regulated oncogene activation, providing a potential therapeutic strategy for UCB. Chen et al. provide an m 5 C landscape in bladder cancer and show m 5 C enrichment at oncogene mRNAs that promotes tumour progression. They identify YBX1 as the m 5 C ‘reader’ that recruits ELAVL1 to stabilize mRNAs.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1465-7392 1476-4679 1476-4679
DOI:	10.1038/s41556-019-0361-y