ATXN2-mediated translation of TNFR1 promotes esophageal squamous cell carcinoma via m6A-dependent manner

被引：21

作者：

Li, Rui ^{[1
,2
]}

Zeng, Lingxing ^{[1
,2
]}

Zhao, Hongzhe ^{[1
,2
]}

Deng, Junge ^{[1
,2
]}

Pan, Ling ^{[1
,2
]}

Zhang, Shaoping ^{[1
,2
]}

Wu, Guandi ^{[1
,2
]}

Ye, Ying ^{[1
,2
]}

Zhang, Jialiang ^{[1
,2
]}

Su, Jiachun ^{[1
,2
]}

Zheng, Yanfen ^{[1
,2
]}

Deng, Shuang ^{[1
,2
]}

Bai, Ruihong ^{[1
,2
]}

Zhuang, Lisha ^{[1
,2
]}

Li, Mei ^{[3
]}

Zuo, Zhixiang ^{[1
,2
]}

Lin, Dongxin ^{[1
,2
,4
]}

Zheng, Jian ^{[1
,2
]}

Huang, Xudong ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ Canc Ctr, State Key Lab Oncol South China, 651 Dongfeng East Rd, Guangzhou 510060, Peoples R China

[2] Sun Yat Sen Univ Canc Ctr, Collaborat Innovat Ctr Canc Med, 651 Dongfeng East Rd, Guangzhou 510060, Peoples R China

[3] Sun Yat Sen Univ Canc Ctr, Dept Pathol, Guangzhou 510060, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Sun Yat Sen Univ Canc Ctr, Dept Etiol & Carcinogenesis, Natl Canc Ctr,Natl Clin Res Ctr,Canc Hosp, 651 Dongfeng East Rd, Guangzhou 510060, Peoples R China

来源：

MOLECULAR THERAPY | 2022年 / 30卷 / 03期

基金：

国家重点研发计划;

关键词：

NF-KAPPA-B; MESSENGER-RNA METHYLATION; TUMOR-NECROSIS-FACTOR; RECEPTOR SUPERFAMILY; CANCER; ACTIVATION; RISK; PROTEINS; ATAXIN-2; ALPHA;

D O I：

10.1016/j.ymthe.2022.01.006

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

N-6-methyladenosine (m(6)A) is the most prevalent RNA modifi- cation, and the effect of its dysregulation on esophageal squamous cell carcinoma (ESCC) development remains unclear. Here, by performing transcriptome-wide m(6)A sequencing in 16 ESCC tissue samples, we identified the key roles of m(6)A in TNFRSF1A (also known as TNFR1)-mediated MAPK and NF-kappa B activation in ESCC. Mechanistically, a functional protein involved in m(6)A methylation, ATXN2, is identified that augments the translation of TNFRSF1A by binding to m(6)A-modified TNFRSF1A mRNA. Upregulation of the TNFRSF1A protein level, a vital upstream switch for TNFRSF1A-mediated signaling events, activates the NF-kappa B and MAPK pathways and thus promotes ESCC development. Furthermore, TNFRSF1A m(6)A modifications and protein levels are upregulated in ESCC, and high levels of TNFRSF1A m(6)A and protein are correlated with poor ESCC patient survival. These results collectively indicate that the m(6)A-TNFRSF1A axis is critical for ESCC development and thus may serve as a potential drug gable target.

引用

页码：1089 / 1103

页数：15

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