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表观遗传甲基化修饰在肝细胞癌中作用的研究进展

Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.

作者信息

Wang Jing, Gao Wenyue, Yu Hongbo, Xu Yuting, Bai Changchuan, Cong Qingwei, Zhu Ying

机构信息

Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People's Republic of China.

Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People's Republic of China.

出版信息

J Hepatocell Carcinoma. 2024 Jun 17;11:1143-1156. doi: 10.2147/JHC.S458734. eCollection 2024.

Abstract

Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.

摘要

肝细胞癌(HCC)是原发性肝癌的主要形式,其预后较差且死亡率高。HCC肿瘤发生的一个关键因素是表观遗传学,特别是通过甲基化对基因表达的调控。这个过程在很大程度上依赖于修饰甲基化的蛋白质的作用,包括甲基转移酶、它们相关的结合蛋白和去甲基化酶。这些蛋白质是关键的调节因子,通过调节酶及其相应的结合蛋白来协调甲基化过程。这种协调促进了基因甲基化位点的读取、结合、检测和催化。甲基化显著影响HCC的发生、增殖、侵袭和预后。此外,甲基化修饰及其调控机制在HCC癌干细胞中激活不同的生物学特性,如诱导干细胞的癌样分化。它们还影响HCC中的肿瘤微环境(TME),调节免疫反应,影响HCC患者的化疗耐药性,并通过信号通路反馈促进HCC进展。鉴于甲基化在遗传信息中的重要作用,它有望成为HCC早期检测的潜在工具,以及改善HCC细胞耐药性和促进细胞凋亡的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9c1/11192199/b772ace0984f/JHC-11-1143-g0001.jpg

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