Zhao Yuhao, Yang Mao, Wang Shijia, Abbas Sk Jahir, Zhang Junzhe, Li Yongsheng, Shao Rong, Liu Yingbin
Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, China.
Front Oncol. 2022 Feb 28;12:854773. doi: 10.3389/fonc.2022.854773. eCollection 2022.
Over the past decades, the aberrant epigenetic modification, apart from genetic alteration, has emerged as dispensable events mediating the transformation of pancreatic cancer (PC). However, the understanding of molecular mechanisms of methylation modifications, the most abundant epigenetic modifications, remains superficial. In this review, we focused on the mechanistic insights of DNA, histone, and RNA methylation that regulate the progression of PC. The methylation regulators including writer, eraser and reader participate in the modification of gene expression associated with cell proliferation, invasion and apoptosis. Some of recent clinical trials on methylation drug targeting were also discussed. Understanding the novel regulatory mechanisms in the methylation modification may offer alternative opportunities to improve therapeutic efficacy to fight against this dismal disease.
在过去几十年中,除了基因改变外,异常的表观遗传修饰已成为介导胰腺癌(PC)转化的重要事件。然而,对于最丰富的表观遗传修饰——甲基化修饰的分子机制的理解仍然很肤浅。在这篇综述中,我们聚焦于DNA、组蛋白和RNA甲基化的机制见解,这些甲基化调控着胰腺癌的进展。甲基化调节因子包括写入器、擦除器和读取器,它们参与与细胞增殖、侵袭和凋亡相关的基因表达修饰。还讨论了一些最近针对甲基化药物的临床试验。了解甲基化修饰中的新调控机制可能为提高对抗这种可怕疾病的治疗效果提供新的机会。