Exploration of the mechanism of 5-Methylcytosine promoting the progression of hepatocellular carcinoma

Qiyao Zhang; Zhen Cao; Yuting He; Ziwen Liu; Wenzhi Guo

doi:10.1016/j.tranon.2024.102257

Exploration of the mechanism of 5-Methylcytosine promoting the progression of hepatocellular carcinoma

Transl Oncol. 2024 Dec 27:52:102257. doi: 10.1016/j.tranon.2024.102257. Online ahead of print.

Authors

Qiyao Zhang¹, Zhen Cao², Yuting He³, Ziwen Liu⁴, Wenzhi Guo⁵

Affiliations

¹ Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; General Surgery Department of Peking Union Medical College Peking Union Medical College Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730.
² General Surgery Department of Peking Union Medical College Peking Union Medical College Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730.
³ Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China. Electronic address: fccheyt1@zzu.edu.cn.
⁴ General Surgery Department of Peking Union Medical College Peking Union Medical College Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730. Electronic address: liuziwen@pumch.cn.
⁵ Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China. Electronic address: fccguowz@zzu.edu.cn.

PMID: 39733743
DOI: 10.1016/j.tranon.2024.102257

Abstract

5-Methylcytosine (m5C) is a ubiquitous RNA modification that is closely related to various cellular functions. However, no studies have comprehensively demonstrated the role of m5C in hepatocellular carcinoma (HCC) progression. In this study, six pairs of HCC and adjacent tissue samples were subjected to methylated RNA immunoprecipitation sequencing to identify precise m5C loci. Non-negative matrix factorization (NMF) was used to identify HCC subtypes in TCGA-LIHC cohort. Immune, metabolic, and tumor-related pathways in HCC subtypes with differences in methylation status were analyzed and a prognostic model based on m5C-related genes was constructed. Finally, using RIP and molecular interaction analysis, we demonstrated that YBX1 binds to TPM3 in an m5C dependent manner and regulates HCC progression. Widespread m5C sites were identified and found to be differentially distributed in HCC compared with adjacent tissues. Metabolic processes were inhibited in hypermethylated HCC, whereas immune checkpoint and multiple classical tumor pathways were significantly upregulated. More importantly, we have identified an m5C dependent regulatory axis. The m5C reader YBX1 binds to TPM3 in an M5C dependent manner and promotes the progression of hepatocellular carcinoma. These results provide new evidence for further understanding the comprehensive role of m5C in HCC and the regulatory mechanism of m5C.

Keywords: 5-methylcytosine; HCC; Immunity; Metabolism; Tumor-related pathways; YBX1.