Hsa_circ_0094606 promotes malignant progression of prostate cancer by inducing M2 polarization of macrophages through PRMT1-mediated arginine methylation of ILF3
Yuwei Zhang, Ke Wang, Delin Yang, Fengping Liu, Xinyu Xu, Yangkun Feng, Yang Wang, Sha Zhu, Chaoqun Gu, Jiayi Sheng, Lei Hu, Bin Xu, Yong‐Jie Lu, Ninghan Feng
Abstract
Circular RNA (circRNA), a type of noncoding RNAs, has been demonstrated to act vital roles in tumorigenesis and cancer deterioration. Although tumor-associated macrophages are involved in tumor malignancy, the interactions between circRNAs and tumor-associated macrophages in prostate cancer (PCa) remain 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 protein arginine methyltransferase 1 (PRMT1) in PCa cells, and further functional assays revealed that circ_0094606 promoted the malignant progression of PCa by binding to PRMT1. Moreover, co-immunoprecipitation (Co-IP), glutathione-S-transferase (GST) pull-down and immunofluorescence showed that PRMT1 mediated arginine methylation of ILF3 to stabilize the protein. Bioinformatics analysis combined with data from RNA-binding protein immunoprecipitation and RNA pull-down suggested that ILF3 could stabilize IL-8 mRNA, which promoted the M2 polarization in coculture 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.