FTO mediated ERBB2 demethylation promotes tumor progression in esophageal squamous cell carcinoma cells

被引：0

作者：

Fangfang Zhao

Fangfang Ge

Minghua Xie

Zhenyu Li

Chunbao Zang

Lingsuo Kong

Youguang Pu

Xucai Zheng

Yiao Tan

机构：

[1] University of Science and Technology of China,Department of Cancer Epigenetics Program, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[2] Anhui Provincial Cancer Hospital,Department of Provincial Clinical College

[3] Wannan Medical College,Department of Thoracic Tumor Surgery Department, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[4] University of Science and Technology of China,Department of Radiation Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[5] Anhui Provincial Cancer Hospital,Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[6] University of Science and Technology of China,Department of Head, Neck and Breast Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[7] Anhui Provincial Cancer Hospital,Department of Urology Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine

[8] University of Science and Technology of China,undefined

[9] Anhui Provincial Cancer Hospital,undefined

[10] University of Science and Technology of China,undefined

[11] Anhui Provincial Cancer Hospital,undefined

[12] University of Science and Technology of China,undefined

[13] Anhui Provincial Cancer Hospital,undefined

来源：

Clinical & Experimental Metastasis | 2022年 / 39卷

关键词：

Esophageal squamous cell carcinoma; N; -methyladenosine (m; A) modification; FTO; ERBB2; YTHDF1;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

N6-methyladenosine (m6A) is the most prevalent and internal modification that occurs in the messenger RNAs of eukaryotes. However, knowledge of the impact of these modifications on gene expression regulation remains limited. By using the in vitro MeRIP-seq and RNA-seq assays, we discovered that the mRNA demethylase FTO was significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells. Furthermore, by using transcriptome-wide m6A-seq and RNA-seq assays, we identified ERBB2 is the target of FTO, which acts in concert in ESCC tumorigenesis and metastasis. Moreover, loss and gain functional studies suggested that the m6A reader YTHDF1 stabilizes ERBB2 mRNA via decoding the m6A modification. All these results uncovered a new signaling cascade, including FTO, YTHDF1, and ERBB2, which finely regulates the ESCC progression.

引用

页码：623 / 639

页数：16

共 351 条

[1] He C(2010)Grand challenge commentary: RNA epigenetics? Nat Chem Biol 6 863-865
[2] Desrosiers R(1974)Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells Proc Natl Acad Sci USA 71 3971-3975
[3] Friderici K(1975)Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells Proc Natl Acad Sci USA 72 2012-2016
[4] Rottman F(1977)Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells J Mol Biol 115 695-714
[5] Lavi S(2012)Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq Nature 485 201-206
[6] Shatkin AJ(1975)Chemistry and biology of macromolecular inhibitors from yeast acting on proteinases A and B, and carboxypeptidase Y Adv Enzyme Regul 13 125-134
[7] Schibler U(2015)N(6)-Methyladenosine modulates Messenger RNA translation efficiency Cell 161 1388-1399
[8] Kelley DE(1995)Classical and novel approaches to the detection and localization of the numerous modified nucleotides in eukaryotic ribosomal RNA Biochimie 77 22-29
[9] Perry RP(1990)The numerous modified nucleotides in eukaryotic ribosomal RNA Prog Nucleic Acid Res Mol Biol 39 241-303
[10] Dominissini D(1995)Accurate and efficient N-6-adenosine methylation in spliceosomal U6 small nuclear RNA by HeLa cell extract in vitro Nucleic Acids Res 23 2421-2426

← 1 2 3 4 5 6 7 8 9 10 →