2. Academic Validation
  3. The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma

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

  • J Clin Invest. 2023 Aug 29;e170173. doi: 10.1172/JCI170173.
Kang Li 1,  Jie Chen 2,  Caihua Zhang 1,  Maosheng Cheng 1,  Shuang Chen 1,  Wei Song 3,  Chunlong Yang 1,  Rongsong Ling 4,  Zhi Chen 1,  Xiaocheng Wang 1,  Gan Xiong 1,  Jieyi Ma 1,  Yan Zhu 1,  Quan Yuan 3,  Qi Liu 5,  Liang Peng 6,  Qianming Chen 7,  Demeng Chen 1
Affiliations

Affiliations

  • 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.
PMID: 37643007 DOI: 10.1172/JCI170173
Abstract

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.

Keywords

Cell Biology; Epigenetics; Head and neck cancer; Oncology.

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