5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs

Xin Chen, Ang Li, Bao Fa Sun, Ying Yang, Ya Nan Han, Xun Yuan, Ri Xin Chen, Wen Su Wei, Yanchao Liu, Chun Chun Gao, Yu Sheng Chen, Mengmeng Zhang, Xiao Dan Ma, Zhuo Wei Liu, Jun Hang Luo, Cong Lyu, Hai Lin Wang, Jinbiao Ma, Yong Liang Zhao, Fang-Jian Zhou & 3 others Ying Huang, Dan Xie, Yun Gui Yang

Research output: Contribution to journalArticle

Abstract

Although 5-methylcytosine (m5C) 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 m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C ‘reader’ recognizing m5C-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 m5C 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 m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.

Original languageEnglish (US)
Pages (from-to)978-990
Number of pages13
JournalNature cell biology
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2019

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5-Methylcytosine
Urinary Bladder Neoplasms
Urinary Bladder
RNA
Carcinoma
Oncogenes
Messenger RNA
3' Untranslated Regions
Methylation
Shock
Up-Regulation
Nucleotides
Survival
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cell Biology

Cite this

Chen, X., Li, A., Sun, B. F., Yang, Y., Han, Y. N., Yuan, X., ... Yang, Y. G. (2019). 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nature cell biology, 21(8), 978-990. https://doi.org/10.1038/s41556-019-0361-y

5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. / 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.

In: Nature cell biology, Vol. 21, No. 8, 01.08.2019, p. 978-990.

Research output: Contribution to journalArticle

Chen, X, Li, A, Sun, BF, Yang, Y, Han, YN, Yuan, X, Chen, RX, Wei, WS, Liu, Y, Gao, CC, Chen, YS, Zhang, M, Ma, XD, Liu, ZW, Luo, JH, Lyu, C, Wang, HL, Ma, J, Zhao, YL, Zhou, F-J, Huang, Y, Xie, D & Yang, YG 2019, '5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs', Nature cell biology, vol. 21, no. 8, pp. 978-990. https://doi.org/10.1038/s41556-019-0361-y
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. / 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. In: Nature cell biology. 2019 ; Vol. 21, No. 8. pp. 978-990.
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