Pan-Cancer Analysis of Molecular Characteristics and Oncogenic Role of PRMT5 in Human Cancers

Abstract Background Accumulating evidence supports the correlation of protein arginine methyltransferase 5 (PRMT5) and cancers development. However, the expression and prognostic values of PRMT5 in various cancers have not been clarified. Methods Here, based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we performed a pan-cancer analysis to explore the expression profile , prognostic value landscape, relationship with tumor-infiltrating immune cells, and potential molecular mechanisms of PRMT5 in cancer development. Moreover, CCK8, wound healing and transwell assays, and western blotting analysis were conducted to evaluate how PRMT5 affects the proliferation and migration, and expression of related hallmarks in breast cancer cells. Results We found that PRMT5 was upregulated in most cancers and PRMT5 harbored distinct prognostic values across different cancer types. In addition, PRMT5 expression was negatively correlated with CD8 + T cells in tumors of cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC) and Skin Cutaneous Melanoma (SKCM), and positively correlated with the cancer-associated fibroblasts in tumors of adrenocortical carcinoma, CESC, cholangio carcinoma, liver hepatocellular carcinoma, pancreatic adenocarcinoma, and SKCM-Primary. Moreover, the enrichment analysis identified that PRMT5 mechanistically regulated cancers development by acting on DNA and RNA metabolism, and stress response related pathways. By further gene silencing experiment, we confirmed tha t PRMT5 knockdown reduced the proliferative and migrative capacities, as well as the expression of PCNA (proliferating cell nuclear antigen), p21 and HMGB1 (high mobility group box 1 protein) in breast cancer cells. Conclusion Collectively, our pan-cancer study highlighted the importance value of PRMT5 in cancer development and prognosis, and pharmacologic targeting at PRMT5 may provide a novel approach for the treatment of cancers.