Wu Yuting, Pu Xi, Wu Sihui, Zhang Yiran, Fu Shengqiao, Tang Haowen, Wang Xu, Xu Min
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
Department of Radiation Oncology, Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
Cancer Cell Int. 2023 Oct 1;23(1):226. doi: 10.1186/s12935-023-03066-7.
N6-methyladenosine(m6A), is the most abundant post-transcriptional modification of mRNA in biology. When the first nucleotide after the m7G cap is adenosine, it is methylated at the N6 position to form N6,2-O-dimethyladenosine (m6Am). m6Am is a reversible modification located at the first transcribed nucleotide, which is present in about 30% of cellular mRNAs, thus m6Am can have a significant impact on gene expression in the transcriptome. Phosphorylated CTD interaction factor 1(PCIF1), the unique and specific methyltransferase of m6Am, has been shown to affect mRNA stability, transcription, and translation. Several studies have shown that PCIF1 is clearly associated with tumor, viral, and endocrine diseases. Moreover, PCIF1 may be related to the tumor microenvironment, immune cell typing, and programmed cell death protein 1(PD-1) drug resistance. Here, we summarize the mechanism of PCIF1 involvement in mRNA modifications, and outline m6Am modifications and diseases in which PCIF1 is involved. We also summarized the role of PCIF1 in immune and immune checkpoint blockade(ICB) treatment, and predicted the possibility of PCIF1 as a biomarker and therapeutic target.
N6-甲基腺苷（m6A）是生物学中mRNA最丰富的转录后修饰。当m7G帽后的第一个核苷酸是腺苷时，它在N6位置被甲基化，形成N6,2'-O-二甲基腺苷（m6Am）。m6Am是一种位于第一个转录核苷酸处的可逆修饰，存在于约30%的细胞mRNA中，因此m6Am可对转录组中的基因表达产生重大影响。磷酸化CTD相互作用因子1（PCIF1）是m6Am独特且特异的甲基转移酶，已被证明会影响mRNA的稳定性、转录和翻译。多项研究表明，PCIF1与肿瘤、病毒和内分泌疾病明显相关。此外，PCIF1可能与肿瘤微环境、免疫细胞分型和程序性细胞死亡蛋白1（PD-1）耐药性有关。在此，我们总结了PCIF1参与mRNA修饰的机制，并概述了m6Am修饰以及PCIF1所涉及的疾病。我们还总结了PCIF1在免疫和免疫检查点阻断（ICB）治疗中的作用，并预测了PCIF1作为生物标志物和治疗靶点的可能性。
