Published on Feb. 1, 2019 in Cancer Lett volume 442DP - 2019 Feb 1TI - YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA inhepatocellular carcinoma.PG - 252-261LID - S0304-3835(18)30670-0 [pii]LID - 10.1016/j.canlet.2018.11.006 [doi]AB - N(6)-methyladenosin (m(6)A) is one of the most pervasive modification of mRNA ineukaryotes and the m(6)A methyltransferases and demethylases play critical roles inmany types of cancer. However the role of m(6)A-binding proteins in cancer remainselusive. Here we report that the down-regulation of YTHDF2 was specifically inducedby hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression ofYTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK inHCC cells. Mechanistically, YTHDF2 directly bound the m(6)A modification site ofEGFR 3'-UTR to promote the degradation of EGFR mRNA in HCC cells. This is the firstreport showing that YTHDF2 may act as a tumor suppressor to repress cellproliferation and growth via destabilizing the EGFR mRNA in HCC.CI - Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.FAU - Zhong, LiAU - Zhong LAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Liao, DanAU - Liao DAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Zhang, MeifangAU - Zhang MAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Zeng, CuilingAU - Zeng CAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Li, XinchunAU - Li XAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Zhang, RuhuaAU - Zhang RAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.FAU - Ma, HaiqingAU - Ma HAD - Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University,Zhuhai, Guangdong, China. Electronic address: mahaiqing@mail.sysu.edu.cn.FAU - Kang, TiebangAU - Kang TAD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center forCancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronicaddress: kangtb@mail.sysu.edu.cn.LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tDEP - 20181110PL - IrelandTA - Cancer LettJT - Cancer lettersJID - 7600053RN - 0 (3' Untranslated Regions)RN - 0 (RNA, Messenger)RN - 0 (RNA-Binding Proteins)RN - 0 (Tumor Suppressor Proteins)RN - 0 (YTHDF2 protein, human)RN - 1867-73-8 (N6-methyladenosine (m6A))RN - EC 2.7.10.1 (EGFR protein, human)RN - EC 2.7.10.1 (ErbB Receptors)RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)RN - K72T3FS567 (Adenosine)SB - IMMH - 3' Untranslated RegionsMH - Adenosine/*analogs & derivatives/metabolismMH - AnimalsMH - Binding SitesMH - Cell Line, TumorMH - *Cell ProliferationMH - Enzyme ActivationMH - ErbB Receptors/genetics/metabolismMH - Extracellular Signal-Regulated MAP Kinases/metabolismMH - Gene Expression Regulation, NeoplasticMH - HumansMH - Liver Neoplasms/genetics/*metabolism/pathologyMH - MaleMH - Mice, Inbred BALB CMH - Mice, NudeMH - Mitogen-Activated Protein Kinase Kinases/metabolismMH - *RNA StabilityMH - RNA, Messenger/genetics/*metabolismMH - RNA-Binding Proteins/genetics/*metabolismMH - Signal TransductionMH - Tumor BurdenMH - Tumor HypoxiaMH - Tumor Suppressor Proteins/genetics/*metabolismOTO - NOTNLMOT - *EGFROT - *ERKOT - *HCCOT - *YTHDF2OT - *mRNAEDAT- 2018/11/14 06:00MHDA- 2019/11/02 06:00CRDT- 2018/11/14 06:00PHST- 2018/09/04 00:00 [received]PHST- 2018/10/25 00:00 [revised]PHST- 2018/11/05 00:00 [accepted]PHST- 2018/11/14 06:00 [pubmed]PHST- 2019/11/02 06:00 [medline]PHST- 2018/11/14 06:00 [entrez]AID - S0304-3835(18)30670-0 [pii]AID - 10.1016/j.canlet.2018.11.006 [doi]PST - ppublishSO - Cancer Lett. 2019 Feb 1;442:252-261. doi: 10.1016/j.canlet.2018.11.006. Epub 2018Nov 10.</pre></div></body></html>().
PubMed ID: 30423408
DOI: S0304-3835(18)30670-0
Abstract:
N(6)-methyladenosin (m(6)A) is one of the most pervasive modification of mRNA ineukaryotes and the m(6)A methyltransferases and demethylases play critical roles inmany types of cancer. However the role of m(6)A-binding proteins in cancer remainselusive. Here we report that the down-regulation of YTHDF2 was specifically inducedby hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression ofYTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK inHCC cells. Mechanistically, YTHDF2 directly bound the m(6)A modification site ofEGFR 3'-UTR to promote the degradation of EGFR mRNA in HCC cells. This is the firstreport showing that YTHDF2 may act as a tumor suppressor to repress cellproliferation and growth via destabilizing the EGFR mRNA in HCC.CI - Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.