The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma

文献类型： 外文期刊

第一作者： Li, Kang

作者： Li, Kang;Zhang, Caihua;Cheng, Maosheng;Chen, Shuang;Yang, Chunlong;Chen, Zhi;Wang, Xiaochen;Xiong, Gan;Zhu, Yan;Peng, Liang;Chen, Qianming;Chen, Demeng;Chen, Jie;Song, Wei;Yuan, Quan;Ling, Rongsong;Liu, Qi;Peng, Liang;Chen, Qianming

作者机构：

期刊名称：JOURNAL OF CLINICAL INVESTIGATION （ 影响因子：15.9； 五年影响因子：16.7 ）

ISSN： 0021-9738

年卷期： 2023 年 133 卷 20 期

页码：

收录情况： SCI

摘要： PCIF1 can mediate the methylation of N6,2 '-O-dimethyladenosine (m6Am) in mRNA. Yet, the detailed interplay between PCIF1 and the potential cofactors and its pathological significance remain elusive. Here, we demonstrated that PCIF1mediated cap mRNA m6Am modification promoted head and neck squamous cell carcinoma progression both in vitro and in vivo. CTBP2 was identified as a cofactor of PCIF1 to catalyze m6Am deposition on mRNA. CLIP-Seq data demonstrated that CTBP2 bound to similar mRNAs as compared with PCIF1. We then used the m6Am-Seq method to profile the mRNA m6Am site at single-base resolution and found that mRNA of TET2, a well-known tumor suppressor, was a major target substrate of the PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA, and the PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrates the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the m6Am modification in tumor progression.

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