机构：[1]Otorhinolaryngology Hospital, Sun Yat-sen University, Guangzhou, China.[2]Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.[3]State Key Laboratory of Oral Diseases, Sichuan University, chengdu, China.[4]Institute for Advanced Study, Shenzhen University, Shenzhen, China.[5]Rice Research Institute, Key Laboratory of Genetics and Breeding of High Quality Rice in Southern China, Guangzhou, China.[6]Senior Department of Oncology, Fifth Medical Center of PLA General Hospital, Beijing, China.[7]Stomatology Hospital, Zhejiang University School of Medicine, Guangzhou, China.
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 remains elusive. Here, we demonstrated that PCIF1-mediated cap mRNA m6Am modification promoted head and neck squamous cell carcinoma (HNSCC) 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 CTBP2 bound to similar mRNAs as PCIF1. We then utilized m6Am-seq method to profile mRNA m6Am site at single-base resolution and found mRNA of TET2, a well-known tumor suppressor, was a major target substrate of PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA and PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrated the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the m6Am modification in tumor progression.
基金：
National Natural Science
Foundation of China (82173362 and 81872409), Guangdong Basic and Applied Basic
Research Foundation (2019A1515110110), and Project funded by China Postdoctoral
Science Foundation (2022M720175).
第一作者机构：[1]Otorhinolaryngology Hospital, Sun Yat-sen University, Guangzhou, China.
共同第一作者：
通讯作者：
通讯机构：[1]Otorhinolaryngology Hospital, Sun Yat-sen University, Guangzhou, China.[5]Rice Research Institute, Key Laboratory of Genetics and Breeding of High Quality Rice in Southern China, Guangzhou, China.[6]Senior Department of Oncology, Fifth Medical Center of PLA General Hospital, Beijing, China.[7]Stomatology Hospital, Zhejiang University School of Medicine, Guangzhou, China.[*1]Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong, 510080, China.[*2]Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China[*3]Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, NO.8 the east street, Fengtai District, Beijing, 100071, China.[*4]Rice Research Institute, Guangdong Academy of Agricultural Sciences, Key Laboratory of Genetics and Breeding of High Quality Rice in Southern China (Co-construction by Ministry and Province), No. 3, Jinyingdong First Street, Guangzhou 510640, China
推荐引用方式(GB/T 7714)：
Li Kang,Chen Jie,Zhang Caihua,et al.The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma[J].JOURNAL OF CLINICAL INVESTIGATION.2023,133(20):doi:10.1172/JCI170173.
APA：
Li Kang,Chen Jie,Zhang Caihua,Cheng Maosheng,Chen Shuang...&Chen Demeng.(2023).The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma.JOURNAL OF CLINICAL INVESTIGATION,133,(20)
MLA：
Li Kang,et al."The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma".JOURNAL OF CLINICAL INVESTIGATION 133..20(2023)
医学