N6-甲基腺苷在胰腺癌诊断与治疗中的研究进展。
Research advances of N6-methyladenosine in diagnosis and therapy of pancreatic cancer.
机构信息
Department of Laboratory Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
出版信息
J Clin Lab Anal. 2022 Sep;36(9):e24611. doi: 10.1002/jcla.24611. Epub 2022 Jul 15.
BACKGROUND
N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance.
METHODS
Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy".
RESULTS
Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy.
CONCLUSION
Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.
背景
N6-甲基腺苷（m6A）是在腺苷的 N6 位置上添加一个甲基基团，是真核生物 mRNA 中最普遍和丰富的表观遗传修饰。m6A 标记由 m6A 甲基转移酶复合物（“书写器”）添加，由 m6A 去甲基酶（“橡皮擦”）去除，并由 m6A 结合蛋白（“阅读器”）识别。最近的证据表明，m6A 修饰在胰腺癌的发病机制和恶性进展中起着至关重要的作用，在细胞存活、增殖、迁移、侵袭、肿瘤转移和耐药性中发挥作用。
方法
在 Pubmed 和 Web of Science 中使用以下关键词搜索文献：“N6-甲基腺苷”、“胰腺癌”、“表观遗传修饰”、“免疫治疗”。
结果
在经典的 m6A 调节因子中，METTL3、METTL14、WTAP、FTO、YTHDF2、IGF2BP1-3、hnRNPC 和 NKAP 在胰腺癌中上调，而 METTL16 和 ALKBH5 在胰腺癌中下调。m6A 修饰已在胰腺癌治疗中进行了研究。
结论
胰腺癌细胞和患者中失调的 m6A 及其相关因素表明它们作为胰腺癌诊断和靶向治疗的新型生物标志物具有潜在价值。
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