Loss of Histone Methyltransferase Ezh2 Exacerbates Polarization of Macrophages toward M2-Like Phenotypes by Hepatocellular Carcinoma [RNA-Seq]

The roles of histone methytransferase Ezh2 in TAMs of liver cancer still unclear. In this study, an RNA sequencing was performed for samples from bone marrow-derived macrophages (BMDMs) of WT and Ezh2 KO mice upon exposure to conditioned media (CM) from hepatocellular carcinoma (HCC) cell line Hepa1-6. The results demonstrated that the absence of Ezh2 in BMDMs exacerbated M2-like phenotypic changes upon incubation with CM from hepatocellular carcinoma (HCC) cell line. The RNA-sequencing revealed that the M2 gene set was further upregulated in treated BMDMs Ezh2 KO compared to treated BMDMs WT WT and the hallmark of Glycolysis as enriched pathway was identified in BMDMs Ezh2 KO. Additionally, the hallmark of IL-6/JAK/STAT pathway was enriched in CM-treated BMDMs. Collectively, these findings provide evidence that JAK/STAT3 axis is critical for M2-like phenotypic changes and Ezh2 suppresses the shifts of macrophage metabolism toward glycolysis that promotes M2 polarization.