PRMT5-FOXM1 axis activates β-catenin/IL8 signaling to drive angiogenesis of gastric cancer.

Protein arginine methyltransferase 5 (PRMT5) functions as an oncogene to regulate cell proliferation and metastasis in many cancers. However, little is known about the role of PRMT5 in tumor angiogenesis. Here, we reported PRMT5 exhibited pro-angiogenic roles in gastric cancer (GC). We observed PRMT5 expression was markedly correlated with microvessel density in GC. Cytological experiment indicated that PRMT5 overexpression promoted tube formation, proliferation, and migration of Human Umbilical Vein Endothelial Cells. However, PRMT5 depletion or enzymatic inhibition restrained these processes. Our in vivo experiments demonstrated that enzymatic inhibition of PRMT5 suppressed angiogenesis of chicken embryo chorioallantoic membranes and mouse xenograft tumors. Mechanistically, we observed PRMT5 up-regulated IL8 expression through activating β-catenin signaling. Evaluation of PRMT5-induced epigenetic marks revealed that PRMT5 depletion erased H3R8me2s from the promotor of Forkhead Box M1 (FOXM1), and finally decreased IL8 transcription. Our results demonstrated the pro-angiogenic effect of PRMT5-FOXM1-IL8 axis in GC, providing a novel approach of targeting such epigenetic regulators in this deadly disease.