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A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling.
Zhang, Jianong; Wei, Jiangbo; Sun, Rui; Sheng, Haoyue; Yin, Kai; Pan, Yunqian; Jimenez, Rafael; Chen, Sujun; Cui, Xiao-Long; Zou, Zhongyu; Yue, Zhiying; Emch, Michael J; Hawse, John R; Wang, Liguo; He, Housheng Hansen; Xia, Shujie; Han, Bangmin; He, Chuan; Huang, Haojie.
Afiliação
  • Zhang J; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China. Electronic address: hugebo
  • Wei J; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Sun R; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
  • Sheng H; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
  • Yin K; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212002, China.
  • Pan Y; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
  • Jimenez R; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.
  • Chen S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Cui XL; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Zou Z; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Yue Z; Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
  • Emch MJ; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
  • Hawse JR; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
  • Wang L; Department of Computation Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.
  • He HH; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Xia S; Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China.
  • Han B; Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China.
  • He C; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. Electr
  • Huang H; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: huang.haojie@mayo.edu.
Mol Cell ; 83(15): 2692-2708.e7, 2023 08 03.
Article em En | MEDLINE | ID: mdl-37478845
N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, and translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated and positively correlated with poor survival of patients with wild-type p53-expressing prostate cancer (PCa). m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. We further showed that FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs. Therapeutic depletion of FTO-IT1 restored mRNA m6A level and expression of p53 target genes and inhibited PCa growth in mice. Our study identifies FTO-IT1 lncRNA as a bona fide suppressor of the m6A methyltransferase complex and p53 tumor suppression signaling and nominates FTO-IT1 as a potential therapeutic target of cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Longo não Codificante / Neoplasias Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Longo não Codificante / Neoplasias Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article