YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma

被引：278

作者：

Zhong, Li ^{[1
]}

Liao, Dan ^{[1
]}

Zhang, Meifang ^{[1
]}

Zeng, Cuiling ^{[1
]}

Li, Xinchun ^{[1
]}

Zhang, Ruhua ^{[1
]}

Ma, Haiqing ^{[2
]}

Kang, Tiebang ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Oncol, Zhuhni, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2019年 / 442卷

关键词：

YTHDF2; EGFR; mRNA; ERK; HCC; M(6)A; CANCER; N-6-METHYLADENOSINE; TRANSLATION; REVEALS; PROTEIN; DOMAIN;

D O I：

10.1016/j.canlet.2018.11.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

N-6-methyladenosin (m(6)A) is one of the most pervasive modification of mRNA in eukaryotes and the m(6)A methyltransferases and demethylases play critical roles in many types of cancer. However the role of m(6)A-binding proteins in cancer remains elusive. Here we report that the down-regulation of YTHDF2 was specifically induced by hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression of YTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK in HCC cells. Mechanistically, YTHDF2 directly bound the m(6)A modification site of EGFR 3'-UTR to promote the degradation of EGFR mRNA in HCC cells. This is the first report showing that YTHDF2 may act as a tumor suppressor to repress cell proliferation and growth via destabilizing the EGFR mRNA in HCC.

引用

页码：252 / 261

页数：10

共 38 条

[1]

[Anonymous], INT J MOL SCI

[2]

[Anonymous], CANC CELL

[3] Hypoxia and Hypoglycemia synergistically regulate mRNA stability [J].

Carraway, Kristen R. ;

Johnson, Ellen M. ;

Kauffmann, Travis C. ;

Fry, Nate J. ;

Mansfield, Kyle D. .

RNA BIOLOGY, 2017, 14 (07) :938-951

[4] MESSENGER RNA HALF-LIFE MEASUREMENTS IN MAMMALIAN CELLS [J].

Chen, Chyi-Ying A. ;

Ezzeddine, Nader ;

Shyu, Ann-Bin .

RNA TURNOVER IN EUKARYOTES: NUCLEASES, PATHWAYS AND ANAYLSIS OF MRNA DECAY, 2008, 448 :335-357

[5] Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice [J].

Cheng, Jin-Mei ;

Li, Jian ;

Tang, Ji-Xin ;

Hao, Xiao-Xia ;

Wang, Zhi-Peng ;

Sun, Tie-Cheng ;

Wang, Xiu-Xia ;

Zhang, Yan ;

Chen, Su-Ren ;

Liu, Yi-Xun .

CELL CYCLE, 2017, 16 (15) :1404-1413

[6] RNA N6-methyladenosine modification in cancers: current status and perspectives [J].

Deng, Xiaolan ;

Su, Rui ;

Weng, Hengyou ;

Huang, Huilin ;

Li, Zejuan ;

Chen, Jianjun .

CELL RESEARCH, 2018, 28 (05) :507-517

[7] YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex [J].

Du, Hao ;

Zhao, Ya ;

He, Jinqiu ;

Zhang, Yao ;

Xi, Hairui ;

Liu, Mofang ;

Ma, Jinbiao ;

Wu, Ligang .

NATURE COMMUNICATIONS, 2016, 7

[8] MicroRNA-145: a promising biomarker for hepatocellular carcinoma (HCC) [J].

Duan, Xianchun ;

Hu, Jianpeng ;

Wang, Yongzhong ;

Gao, Jiarong ;

Peng, Daiyin ;

Xia, Lunzhu .

GENE, 2014, 541 (01) :67-68

[9] N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs [J].

Fry, Nate J. ;

Law, Brittany A. ;

Ilkayeva, Olga R. ;

Holley, Christopher L. ;

Mansfield, Kyle D. .

RNA, 2017, 23 (09) :1444-1455

[10] Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis [J].

Hsu, Phillip J. ;

Zhu, Yunfei ;

Ma, Honghui ;

Guo, Yueshuai ;

Shi, Xiaodan ;

Liu, Yuanyuan ;

Qi, Meijie ;

Lu, Zhike ;

Shi, Hailing ;

Wang, Jianying ;

Cheng, Yiwei ;

Luo, Guanzheng ;

Dai, Qing ;

Liu, Mingxi ;

Guo, Xuejiang ;

Sha, Jiahao ;

Shen, Bin ;

He, Chuan .

CELL RESEARCH, 2017, 27 (09) :1115-1127

← 1 2 3 4 →