| Literature DB >> 34995801 |
Rui Li1, Lingxing Zeng1, Hongzhe Zhao1, Junge Deng1, Ling Pan1, Shaoping Zhang1, Guandi Wu1, Ying Ye1, Jialiang Zhang1, Jiachun Su1, Yanfen Zheng1, Shuang Deng1, Ruihong Bai1, Lisha Zhuang1, Mei Li2, Zhixiang Zuo1, Dongxin Lin3, Jian Zheng4, Xudong Huang5.
Abstract
N6-methyladenosine (m6A) is the most prevalent RNA modification, and the effect of its dysregulation on esophageal squamous cell carcinoma (ESCC) development remains unclear. Here, by performing transcriptome-wide m6A sequencing in 16 ESCC tissue samples, we identified the key roles of m6A in TNFRSF1A (also known as TNFR1)-mediated MAPK and NF-κB activation in ESCC. Mechanistically, a functional protein involved in m6A methylation, ATXN2, is identified that augments the translation of TNFRSF1A by binding to m6A-modified TNFRSF1A mRNA. Upregulation of the TNFRSF1A protein level, a vital upstream switch for TNFRSF1A-mediated signaling events, activates the NF-κB and MAPK pathways and thus promotes ESCC development. Furthermore, TNFRSF1A m6A modifications and protein levels are upregulated in ESCC, and high levels of TNFRSF1A m6A and protein are correlated with poor ESCC patient survival. These results collectively indicate that the m6A-TNFRSF1A axis is critical for ESCC development and thus may serve as a potential druggable target.Entities:
Keywords: ATXN2; NF-кB and MAPK activation; RNA N6-methyladenosine; TNFR1; esophageal squamous cell carcinoma
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Year: 2022 PMID： 34995801 PMCID： PMC8899599 DOI： 10.1016/j.ymthe.2022.01.006
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 12.910