PCIF1, or phosphorylated CTD interaction factor 1, is the unique and specific methyltransferase of N6,2-O-dimethyladenosine (m6Am). m6Am is a reversible modification present in about 30% of cellular mRNAs when the first nucleotide after the m7G cap is adenosine, significantly impacting gene expression in the transcriptome. PCIF1 has been shown to affect mRNA stability, transcription, and translation, and is involved in various biological processes and diseases [1].

Nuclease technology-mediated depletion of PCIF1 in human colorectal cancer (CRC) cells leads to loss of cell migration, invasion, and colony formation in vitro and tumor growth in athymic mice. In murine CRC cells, Pcif1 knockout inhibits tumor growth in immunocompetent mice and enhances the effects of anti-PD-1 antibody treatment [2]. In gastric cancer, silence of PCIF1 inhibits the proliferation and invasion of gastric cancer cells, and suppresses tumor growth and metastasis in mouse model [3]. Loss of m6Am methyltransferase PCIF1 attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models [4].

In conclusion, PCIF1-mediated m6Am modification is crucial for multiple biological processes. Pcif1 knockout mouse models have revealed its role in promoting tumorigenesis in CRC and gastric cancer, and in regulating periodontal inflammation. These findings suggest PCIF1 could be a potential therapeutic target for treating related diseases.

References:

1. Wu, Yuting, Pu, Xi, Wu, Sihui, Wang, Xu, Xu, Min. 2023. PCIF1, the only methyltransferase of N6,2-O-dimethyladenosine. In Cancer cell international, 23, 226. doi:10.1186/s12935-023-03066-7. https://pubmed.ncbi.nlm.nih.gov/37779183/

2. Wang, Lingling, Wu, Lujing, Zhu, Zhouting, Wang, Yinsheng, Rana, Tariq M. 2022. Role of PCIF1-mediated 5'-cap N6-methyladeonsine mRNA methylation in colorectal cancer and anti-PD-1 immunotherapy. In The EMBO journal, 42, e111673. doi:10.15252/embj.2022111673. https://pubmed.ncbi.nlm.nih.gov/36514940/

3. Zhuo, Wei, Sun, Meng, Wang, Kun, Yi, Chengqi, Zhou, Tianhua. 2022. m6Am methyltransferase PCIF1 is essential for aggressiveness of gastric cancer cells by inhibiting TM9SF1 mRNA translation. In Cell discovery, 8, 48. doi:10.1038/s41421-022-00395-1. https://pubmed.ncbi.nlm.nih.gov/35597784/

4. Song, W, Liu, L, Liang, H, Chen, D, Yuan, Q. 2024. m6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation. In Journal of dental research, 103, 1130-1140. doi:10.1177/00220345241271078. https://pubmed.ncbi.nlm.nih.gov/39290151/