The promoting role of protein arginine methyltransferase 1 in cervical cancer: Mechanisms of angiogenesis and immune evasion.

OBJECTIVE: Cervical cancer (CC) is a leading factor in cancer-associated mortality among women worldwide. Protein arginine methyltransferase 1 (PRMT1) is involved in tumor growth, metastasis, and immune regulation in various types of cancer. However, the specific role of PRMT1 in CC remains unclear. This study aims to assess the expression pattern of PRMT1 in CC and its effects on tumor growth, angiogenesis, immune response, and metastasis. MATERIAL AND METHODS: We used quantitative reverse-transcription polymerase chain reaction and Western blot to detect the expression of PRMT1 in mouse tumor tissues and normal cervical tissues and the differential expression of PRMT1 in human cervical epithelial cells (HCerEpiC) and CC cell lines (HeLa). An ectopic CC mouse model was established and treated with anti-PRMT1 antibody or PRMT1 recombinant protein to evaluate PRMT1 expression in tumor tissues, tumor volume, weight, and histological changes. Transwell and tube formation assays were performed to assess the effects of PRMT1 on CC cell migration, invasion, and endothelial cell tube formation. The regulation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) signaling pathway in HeLa cells by PRMT1 was also investigated using PicoGreen staining and Western blot analysis. RESULTS: The expression of PRMT1 was noticeably higher in tumor tissues than in normal tissues (P < 0.001) as well as in HeLa than in HCerEpiC (P < 0.001). In the mouse model, anti-PRMT1 treatment significantly inhibited tumor growth and reduced PRMT1 expression (P < 0.001). Treatment with PRMT1 recombinant protein promoted tumor growth and increased PRMT1 expression (P < 0.001). Histological analysis revealed that anti-PRMT1 treatment led to tumor cell shrinkage, nuclear condensation, and tissue necrosis, whereas PRMT1 recombinant protein treatment promoted cell proliferation and nuclear enlargement. Moreover, anti-PRMT1 treatment suppressed the expression of angiogenesis-related markers (a-smooth muscle actin, Cluster of differentiation 31, and glucose transporter 1) and significantly increased CD8+ immune cell infiltration, while PRMT1 recombinant protein enhanced angiogenesis and inhibited CD8 expression (P < 0.001). Knockdown of PRMT1 (Sh-PRMT1) significantly inhibited HeLa cell migration and invasion, while overexpression of PRMT1 (Ov-PRMT1) significantly promoted these processes (P < 0.001). Tube formation assays showed that Sh-PRMT1 treatment suppressed tube formation in human umbilical vein endothelial cells, whereas Ov-PRMT1 increased the number of formed tubes (P < 0.001). Finally, Sh-PRMT1 treatment significantly increased the activation of the cGAS-STING signaling pathway, while Ov-PRMT1 suppressed its activity (P < 0.001). CONCLUSION: PRMT1 promotes CC progression by enhancing tumor growth, angiogenesis, and immune evasion, partly by regulating the cGAS-STING pathway. Hence, it may serve as a potential therapeutic target.