Hsa_circ_0094606 promotes malignant progression of prostate cancer by inducing M2 polarization of macrophages through PRMT1-mediated arginine methylation of ILF3.

Circular RNA (circRNA), a type of noncoding RNAs, has been demonstrated to act vital roles in tumorigenesis and cancer deterioration. While tumor-associated macrophages (TAMs) involved in tumor malignancy, the interactions between circRNAs and TAMs in prostate cancer (PCa) remains unclear. In the present study, we found that hsa_circ_0094606 (subsequently named circ_0094606) could promote proliferation, epithelial mesenchymal transition (EMT) as well as migration of PCa cells through cell viability and migration assays and the determination of EMT markers. Mass spectrometry analysis after RNA pull-down experiment identified that circ_0094606 bound to PRMT1 in PCa cells, and further functional assays revealed that circ_0094606 promoted malignant progression of PCa by binding to PRMT1. Moreover, Co-IP, GST pull-down and Immunofluorescence showed that PRMT1 mediated arginine methylation of ILF3 to stabilize the protein. Bioinformatics analysis combined with data from RIP and RNA-pull down suggested that ILF3 could stabilize IL-8 mRNA, which promoted the M2 polarization in co-culture study. Finally, in vivo experiments showed that circ_0094606 subserve PCa growth and promoted the M2 polarization of macrophages through the PRMT1/ILF3/IL-8 regulation pathway, supporting circ_0094606 as a potential novel effective target for PCa treatment.