Arginine demethylation of Serine/Arginine‐rich splicing factor 1 enhances miRNA enrichment in small extracellular vesicles derived from pancreatic ductal adenocarcinoma cells

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 6, 2025

Small extracellular vesicles (sEVs) are enriched in certain miRNAs, impacting the progression of pancreatic ductal adenocarcinoma (PDAC). The mechanisms involved selective sEV miRNA enrichment remain to be elucidated. We recently reported that Serine/Arginine-rich splicing factor 1 (SRSF1) regulates PDAC cells. SRSF1 is an onco-protein overexpressed PDAC, and its function dictated by posttranslational modifications such as phosphorylation arginine methylation. objective this study was examine role methylation SRSF1-mediated Treatment cells with protein methyltransferase inhibitors AMI-5 EPZ015666, but not inhibitor SRPIN340, selectively enhanced level miR-1246, a known highly sEVs. Consistently, overexpression mutant three residues R93, R97, R109 being replaced lysinaugmented miR-1246 levels both wild-type SRSF1-knockdown PANC-1 Interestingly, binding significantly reduced overexpressing SRSF1, which further confirmed using purified proteins. demonstrate demethylation reduces SRSF1-miRNA enhances enrichment, providing novel insight into opening up new avenues investigation on biology PDAC.

Language: Английский

Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3958 - 3958

Published: April 2, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with low 5-year overall survival rate. It the third-leading cause of cancer-related deaths in United States. The lack robust therapeutics, absence effective biomarkers for early detection, and aggressive nature tumor contribute to high mortality rate PDAC. Notably, outcomes recent immunotherapy targeted therapy against PDAC remain unsatisfactory, indicating need novel therapeutic strategies. One newly described molecular features altered expression protein arginine methyltransferases (PRMTs). PRMTs are group enzymes known methylate residues both histone non-histone proteins, thereby mediating cellular homeostasis biological systems. Some PRMT be overexpressed that promotes progression chemo-resistance via regulating gene transcription, metabolic processes, RNA metabolism, epithelial mesenchymal transition (EMT). Small-molecule inhibitors currently under clinical trials can potentially become new generation anti-cancer drugs. This review aims provide an overview current understanding PDAC, focusing on their pathological roles potential as targets.

Language: Английский

The influence of melanoma extracellular vesicles on benign melanocytes: a role for PRAME in modulation of the tumor microenvironment

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский