Protein Arginine Methyltransferases 5 (PRMT5) affect Multiple Stages of Autophagy and Modulate Autophagy-related Genes in Controlling Breast Cancer Tumorigenesis.

Abstract

Autophagy disorders are linked to human cancer, and the details of their mechanisms remain unclear. To investigate the regulatory role of PRMT5 in the autophagy of breast cancer cells. Human breast adenocarcinoma cell lines (MDA-MB-231, MCF7) were cultured. Plasmids of overexpression and down-regulation of PRMT5 were transfected into MDA-MB-231 and MCF7 cells. The MTT assay was used to determine the proliferation of MDA-MB-231 and MCF7 cells. A western blotting assay was used to verify the expression of autophagy-associated molecules. Immunofluorescence was applied to observe the expression of GFP-LC3. The expression of PRMT5 decreased the sensitivity to rapamycin and nutrient deprivation. PRMT5 acts as an oncogene to promote cell proliferation and influences migration and stamness. PRMT5 expression elevated the autophagic activity initiated by EBSS and Rapamycin. PRMT5 was necessary and sufficient to enhance stress-induced autophagy. PRMT5 could improve several autophagy- related gene expressions. Atg5 expression could be regulated by activating the PRMT5 and PDCD4 molecules. The PRMT5 molecule could mediate the regulation of ULK1 expression. PRMT5 influenced multiple stages of autophagy in controlling autophagy and tumorigenesis. Autophagy-related PRMT5 might be a respected target for therapeutic interventions in cancers. This study would provide new ideas for treating and selecting breast cancer targets.