Pcif1, or Phosphorylated CTD interaction factor 1, is the unique and specific methyltransferase of N6,2-O-dimethyladenosine (m6Am) [1]. m6Am is a reversible modification at the first transcribed nucleotide in about 30% of cellular mRNAs, influencing gene expression in the transcriptome. Pcif1-mediated m6Am modification can impact mRNA stability, transcription, and translation, and is thus of great biological importance [1].

Nuclease technology-mediated depletion of Pcif1 in human colorectal cancer (CRC) cells led to loss of cell migration, invasion, and colony formation in vitro and tumor growth in athymic mice. In murine CRC cells, Pcif1 knockout inhibited tumor growth in immunocompetent mice and enhanced the effects of anti-PD-1 antibody treatment [2]. In gastric cancer cells, silence of Pcif1 inhibited cell proliferation and invasion, and suppressed tumor growth and metastasis in a mouse model [4]. Also, loss of Pcif1 attenuated periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models [3].

In conclusion, Pcif1 plays a crucial role in various biological processes mainly through its m6Am methyltransferase activity. Pcif1 knockout or knockdown in mouse models has revealed its significance in diseases such as colorectal cancer, gastric cancer, and periodontal inflammation, suggesting its potential as a biomarker and therapeutic target in these disease areas.