EHF promotes liver cancer progression by meditating IL-6 secretion through transcription regulation of KDM2B in TAMs

Abstract

Background

Macrophages are key immune cell types in liver, which are thought to be involved in tumor development. Recent studies indicated that TAMs exhibit M2 phenotypes. However, the mechanism of macrophages related to tumor progression in liver cancer is largely unknown. We aim to investigate the mechanism of EHF in TAMs associated with liver cancer progression.

Methods

The differently expressed genes of M0, M1, and M2 macrophages were analyzed by RNA sequencing. Cytokine array was used to detect the differently expressed cytokines in M2 macrophages. We performed CUT-Tag analysis for the identification of promoter regions that interacting with EHF protein. ChIP and luciferase analysis were used to verify the interaction between EHF and KDM2B.

Results

EHF was overexpressed in M2 macrophages. Knockdown of EHF in M2 macrophages could inhibit migration and invasion of MHCC97-L cells co-cultured with M2 macrophages in vitro and in vivo. The level of IL-6 was decreased in M2 macrophages with lower expression of EHF. EHF could bind the promoter region of KDM2B. The transcription level of KDM2B was down-regulated by knockdown of EHF in M2 macrophages. The results of this study indicated that EHF could promote liver cancer cell metastasis by IL-6 through regulating the transcription level of KDM2B in M2 macrophages.

Conclusion

Our study revealed a novel aspect of macrophages in liver cancer and showed EHF could be a promising therapeutic target of liver cancer.