| First Author | Li K | Year | 2023 |
| Journal | J Clin Invest | Volume | 133 |
| Issue | 20 | PubMed ID | 37643007 |
| Mgi Jnum | J:341638 | Mgi Id | MGI:7542890 |
| Doi | 10.1172/JCI170173 | Citation | Li K, et al. (2023) The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma. J Clin Invest 133(20) |
| abstractText | 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 PCIF1-mediated 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. |
