PRMT3 promotes tumorigenesis by methylating and stabilizing HIF1α in colorectal cancer

• DOI: 10.1038/s41419-021-04352-w
• Publication Date: 2021-11-09T13:03:39Z
• Authors: Xin Zhang; Kexin Wang; Xingbo Feng; Jian Wang; Yali Chu; Chunmeng Jia; Qingsi He; Cheng Chen
• Keywords: 0301 basic medicine; Protein-Arginine N-Methyltransferases; QH573-671; Carcinogenesis; Cell Cycle; Hypoxia-Inducible Factor 1, alpha Subunit; Transfection; Article; 3. Good health; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Female; Cytology; Colorectal Neoplasms; Signal Transduction

AbstractAbnormal angiogenesis occurs during the growth of solid tumors resulting in increased vascular permeability to fluids and metastatic cancer cells. Anti-angiogenesis therapy for solid tumors is effective in the treatment of cancer patients. However, the efficacy of anti-angiogenesis therapy is limited by drug resistance. The findings of the current study showed that HIF1α R282 is methylated by PRMT3, which is necessary for its stabilization and oncogene function. Analysis showed that PRMT3-mediated tumorigenesis is HIF1α methylation-dependent. A novel therapeutic molecule (MPG-peptide) was used to inhibit HIF1α expression. These findings provided information on PRMT3 signaling pathway and HIF1/VEGFA signaling pathway and offer a novel therapeutic strategy for colorectal cancer, mainly for treatment of anti-angiogenesis resistance patients.