PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis

Abstract

Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle, which is called the Warburg effect. However, the detailed mechanisms of abnormal activation of the glycolysis pathway in colorectal cancer are largely unknown. In this study, we reveal that the protein arginine methyltransferase 1 (PRMT1) promotes glycolysis, proliferation, and tumorigenesis in CRC cells. Mechanistically, PRMT1-mediated arginine asymmetric dimethylation modification of phosphoglycerate kinase 1 (PGK1, the first ATP-producing enzyme in glycolysis) at R206 (meR206-PGK1) enhances the phosphorylation level of PGK1 at S203 (pS203-PGK1), which inhibits mitochondrial function and promotes glycolysis. We found that PRMT1 and meR206-PGK1 expression were positively correlated with pS203-PGK1 expression in tissues from colorectal cancer patients. Furthermore, we also confirmed that meR206-PGK1 expression is positively correlated with the poor survival of patients with colorectal cancer. Our findings show that PRMT1 and meR206-PGK1 may become promising predictive biomarkers for the prognosis of patients with CRC and that arginine methyltransferase inhibitors have great potential in colorectal cancer treatment.

The Interplay of Acetylation and Ubiquitination Controls PRMT1 Homeostasis

“…PRMT1 has largely been characterized as a critical driver of breast cancer through its roles in transcription (Gao et al, 2016; Li et al, 2021) and methylation of estrogen and progesterone receptors (Le Romancer et al, 2008; Malbeteau et al, 2020) as well as regulation of epidermal growth factor receptor and Wnt signaling pathways (Suresh et al, 2022). Dysregulation of these processes has also been shown to drive progression in other cancers, such as colorectal cancer (Liu et al, 2024; Zhang et al, 2023b), melanoma (Tao et al, 2024), hepatocellular carcinoma (Jiang et al, 2023b), prostate cancer (Tang et al, 2022), pancreatic cancer (Nguyen et al, 2024), leukemia (Cheung et al, 2007; Shia et al, 2012), and non-small cell lung cancer (Avasarala et al, 2015). More recently, PRMT1 has been linked to cancer metabolism through promoting glycolysis in hepatocellular carcinoma and colorectal cancer (Li et al, 2023; Liu et al, 2024), as well as fatty acid metabolism in hepatocellular carcinoma and breast cancer (Yamamoto et al, 2024; Yan et al, 2024).…”

“…Dysregulation of these processes has also been shown to drive progression in other cancers, such as colorectal cancer (Liu et al, 2024; Zhang et al, 2023b), melanoma (Tao et al, 2024), hepatocellular carcinoma (Jiang et al, 2023b), prostate cancer (Tang et al, 2022), pancreatic cancer (Nguyen et al, 2024), leukemia (Cheung et al, 2007; Shia et al, 2012), and non-small cell lung cancer (Avasarala et al, 2015). More recently, PRMT1 has been linked to cancer metabolism through promoting glycolysis in hepatocellular carcinoma and colorectal cancer (Li et al, 2023; Liu et al, 2024), as well as fatty acid metabolism in hepatocellular carcinoma and breast cancer (Yamamoto et al, 2024; Yan et al, 2024). PRMT1 has also been shown to play an important roles beyond oncology, including in cardiovascular disease (Couto e Silva et al, 2020), diabetes (Iwasaki, 2024) and neurodegenerative diseases (Angelopoulou et al, 2023) such as amyotrophic lateral sclerosis (Aikio et al, 2021).…”