The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma
文献类型： 外文期刊
作者： Li, Kang 1 ; Chen, Jie 2 ; Zhang, Caihua 1 ; Cheng, Maosheng 1 ; Chen, Shuang 1 ; Song, Wei 3 ; Yang, Chunlong 1 ; Ling, Rongsong 4 ; Chen, Zhi 1 ; Wang, Xiaochen 1 ; Xiong, Gan 1 ; Ma, Jieyi 1 ; Zhu, Yan 1 ; Yuan, Quan 3 ; Liu, Qi 5 ; Peng, Liang 1 ; Chen, Qianming 1 ; Chen, Demeng 1 ;
作者机构： 1.Sun Yat Sen Univ, Otorhinolaryngol Hosp, Affiliated Hosp 1, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Hosp Stomatol, Guanghua Sch Stomatol, Guangdong Prov Key Lab Stomatol, Guangzhou, Peoples R China
3.Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, Chengdu, Peoples R China
4.Shenzhen Univ, Inst Adv Study, Shenzhen, Peoples R China
5.Guangdong Acad Agr Sci, Rice Res Inst, Key Lab Genet & Breeding High Qual Rice Southern C, 3 Jinyingdong First St, Guangzhou 510640, Peoples R China
6.Peoples Liberat Army Gen Hosp, Med Ctr 5, Senior Dept Oncol, 8 East St, Beijing 100071, Peoples R China
7.Zhejiang Univ, Sch Med, Stomatol Hosp, Engn Res Ctr Oral Biomat & Devices Zhejiang Prov,K, Hangzhou 310000, Peoples R China
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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