METTL9,也称为Methyltransferase-like 9,是一种与DNA、RNA和蛋白质甲基化相关的甲基转移酶。甲基化是一种常见的细胞成分化学修饰,影响生物过程,包括转录、RNA处理和蛋白质动力学。尽管异常表达的甲基转移酶可以导致各种疾病,包括癌症,但对甲基转移酶与癌症之间的关系了解甚少。
METTL9在多种癌症中发挥重要作用,包括结直肠癌、胃癌和肝细胞癌。在结直肠癌中,circ-METTL9是一种来自METTL9基因的环状RNA,通过海绵miR-551b-5p来上调CDK6的表达,从而促进细胞周期进展和肿瘤生长[1]。在胃癌中,METTL9的表达升高与肿瘤的腹膜扩散相关,METTL9的敲低可以显著抑制肿瘤细胞的迁移和侵袭[3]。在肝细胞癌中,METTL9的表达升高与不良预后相关,METTL9的敲低可以抑制肿瘤细胞的增殖和迁移[4]。
此外,METTL9还与其他疾病相关。在骨量减少和肌肉减少症患者中,METTL9是7个候选基因之一,可能作为诊断的潜在生物标志物[2]。在败血症中,METTL9是9个关键基因之一,与免疫状态相关,可能作为诊断和治疗的潜在分子靶点[5]。在帕金森病中,METTL9通过促进NF-κB/ NLRP3信号通路,抑制炎症反应和神经元焦亡,从而改善运动功能障碍[6]。
综上所述,METTL9是一种重要的甲基转移酶,参与调控DNA、RNA和蛋白质的甲基化,影响生物过程和疾病发生。METTL9在多种癌症、骨量减少和肌肉减少症、败血症和帕金森病中发挥重要作用。METTL9的研究有助于深入理解甲基化的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Li, Ming, Zhi, Zheng, Jiang, Xuan, Li, Jian-Ming, Sun, Li-Na. . METTL9 derived circular RNA circ-METTL9 sponges miR-551b-5p to accelerate colorectal cancer progression by upregulating CDK6. In Carcinogenesis, 44, 463-475. doi:10.1093/carcin/bgad031. https://pubmed.ncbi.nlm.nih.gov/37158456/
2. Zhou, Xiaoli, Zhao, Lina, Zhang, Zepei, Miao, Jun, Li, Xiaohui. 2024. Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning. In BMC musculoskeletal disorders, 25, 435. doi:10.1186/s12891-024-07555-2. https://pubmed.ncbi.nlm.nih.gov/38831425/
3. Hara, Toshifumi, Tominaga, Yuuki, Ueda, Koji, Yanagihara, Kazuyoshi, Takei, Yoshifumi. 2022. Elevated METTL9 is associated with peritoneal dissemination in human scirrhous gastric cancers. In Biochemistry and biophysics reports, 30, 101255. doi:10.1016/j.bbrep.2022.101255. https://pubmed.ncbi.nlm.nih.gov/35402738/
4. Zheng, Qiuxian, Yang, Qin, Zhou, Jiaming, Zhu, Haihong, Chen, Zhi. 2021. Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions. In Cancer cell international, 21, 330. doi:10.1186/s12935-021-02033-4. https://pubmed.ncbi.nlm.nih.gov/34193146/
5. Tong, Ran, Ding, Xianfei, Liu, Fengyu, Liu, Shaohua, Sun, Tongwen. 2023. Classification of subtypes and identification of dysregulated genes in sepsis. In Frontiers in cellular and infection microbiology, 13, 1226159. doi:10.3389/fcimb.2023.1226159. https://pubmed.ncbi.nlm.nih.gov/37671148/
6. Zhou, Xiang, Zhou, Liang, Sun, Jiayi, Zhang, Juan, Sun, Lei. . Electroacupuncture Alleviates Parkinson's Disease by Promoting METTL9-Catalyzed Histidine Methylation of Nuclear Factor-κВ. In Critical reviews in eukaryotic gene expression, 34, 17-27. doi:10.1615/CritRevEukaryotGeneExpr.2024053243. https://pubmed.ncbi.nlm.nih.gov/39072406/