Jing Wang,1 Wenyue Gao,1 Hongbo Yu,1 Yuting Xu,1 Changchuan Bai,2 Qingwei Cong,1 Ying Zhu1 

1Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People’s Republic of China

Correspondence: Ying Zhu, Email zhuyingsh52@126.com

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.

Keywords: methylation modifying proteins, biomarkers, methyltransferases, HCC tumorigenesis