PRMT1 Integrates Immune Microenvironment and Fatty Acid Metabolism Response in Progression of Hepatocellular Carcinoma

Jia Yan; Ke Xin Li; Lei Yu; Heng Ye Yuan; Zhi Min Zhao; Jing Lin; Chang Shan Wang

doi:10.2147/JHC.S443130

PRMT1 Integrates Immune Microenvironment and Fatty Acid Metabolism Response in Progression of Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2024 Jan 6:11:15-27. doi: 10.2147/JHC.S443130. eCollection 2024.

Authors

Jia Yan^#^{1

2

3}, Ke Xin Li^#², Lei Yu², Heng Ye Yuan², Zhi Min Zhao², Jing Lin^{2

4}, Chang Shan Wang²

Affiliations

¹ School of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.
² College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, People's Republic of China.
³ Medical Experimental Center of Basic Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.
⁴ Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.

^# Contributed equally.

Abstract

Background: Protein arginine methyltransferase (PRMT) family members have important roles in cancer processes. However, its functions in the regulation of cancer immunotherapy of hepatocellular carcinoma (HCC) are incompletely understood. This study aimed to investigate the roles of PRMT1 in HCC.

Methods: Single-cell RNA sequencing (scRNA-seq) and clinicopathological data were obtained and used to explore the diagnostic and prognostic value, cellular functions and roles in immune microenvironment regulation of PRMT1 in HCC. The functions of PRMT1 were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), as well as gene set enrichment analysis (GSEA). TIMER and CIBERSORT were used to analyze the relationships between PRMT1 expression and immune cell infiltration. The STRING database was used to construct a protein-protein interaction (PPI) network.

Results: PRMT1 was aberrantly expressed in HCC, which high expression was associated with tumor progression, worse overall survival (OS) and disease-free survival (DFS) of patients with HCC. PRMT1 was also associated with immune cell infiltration. Moreover, it was specifically expressed in immune cells, including exhausted CD8 T cells, B cells, and mono/macro cells in patients with immunotherapy. The expression of immune checkpoints was significantly increased in the high-PRMT1 expression groups of HCC patients. Regarding biological mechanisms, cell viability, migration and invasion, and the expression of genes related to fatty acid metabolism were suppressed in PRMT1 knockdown HCC cells. Moreover, genes co-expressed with PRMT1 were involved in the fatty acid metabolic process and enriched in fatty and drug-induced liver disease.

Conclusion: Taken together, these results indicate that PRMT1 might exert its oncogenic effects via immune microenvironment regulation and fatty acid metabolism in HCC. Our finding will provide a foundation for further studies and indicate a potential clinical therapeutic target for liver cancer.

Keywords: PRMT1; fatty acid metabolism; prognosis; protein arginine methyltransferase; tumor-infiltrating.

Grants and funding

This work was supported by Natural Science Foundation of Inner Mongolia (2023MS08033), National Natural Science Foundation of China (CN) (grant Nos. 81660024), the Joint Project of Inner Mongolia Medical University (grant Nos. YKD2021LH001), Key Project of Natural Science for Colleges and Universities in Inner Mongolia (grant Nos. NJZZ22686) and Inner Mongolia Medical University Science and Technology Innovation Team (grant Nos. YKD2022TD031).