mAm甲基转移酶PCIF1通过抑制TM9SF1 mRNA翻译对胃癌细胞的侵袭性至关重要。
mAm methyltransferase PCIF1 is essential for aggressiveness of gastric cancer cells by inhibiting TM9SF1 mRNA translation.
作者信息
Zhuo Wei, Sun Meng, Wang Kun, Zhang Lu, Li Kai, Yi Danyang, Li Mengjie, Sun Qiang, Ma Xixi, Liu Wei, Teng Lisong, Yi Chengqi, Zhou Tianhua
机构信息
Department of Cell Biology and Department of Gastroenterology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
出版信息
Cell Discov. 2022 May 21;8(1):48. doi: 10.1038/s41421-022-00395-1.
PCIF1 (phosphorylated CTD interacting factor 1) is the first reported RNA N6,2'-O-dimethyladenosine (mAm) methyltransferase. However, the pathological significance of PCIF1 and mAm modification remains unknown. Here we find that both PCIF1 expression and mAm modification are significantly elevated in gastric cancer tissues. Increased PCIF1 is associated with gastric cancer progression, and predicts poor prognosis. Silence of PCIF1 inhibits the proliferation and invasion of gastric cancer cells, and suppresses tumor growth and metastasis in mouse model. mAm-seq analysis reveals TM9SF1 (transmembrane 9 superfamily member 1) as a target of PCIF1. PCIF1 modifies TM9SF1 mRNA with mAm leading to decreased TM9SF1 translation. TM9SF1 reverses the effects of PCIF1 on gastric cancer cell aggressiveness. Collectively, our work uncovers an oncogenic function of PCIF1, providing insights into the critical role of mAm modification in cancer progression.
PCIF1（磷酸化CTD相互作用因子1）是首个被报道的RNA N6,2'-O-二甲基腺苷（mAm）甲基转移酶。然而，PCIF1和mAm修饰的病理意义仍不清楚。在此我们发现，PCIF1的表达和mAm修饰在胃癌组织中均显著升高。PCIF1的增加与胃癌进展相关，并预示着预后不良。沉默PCIF1可抑制胃癌细胞的增殖和侵袭，并在小鼠模型中抑制肿瘤生长和转移。mAm序列分析显示TM9SF1（跨膜9超家族成员1）是PCIF1的一个靶点。PCIF1通过mAm修饰TM9SF1 mRNA，导致TM9SF1翻译减少。TM9SF1可逆转PCIF1对胃癌细胞侵袭性的影响。总体而言，我们的研究揭示了PCIF1的致癌功能，为mAm修饰在癌症进展中的关键作用提供了见解。
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