Retinoblastoma (RB) is the most common intraocular malignant tumour in infants, and chemotherapy has been the primary therapy method in recent years. PRMT5 is an important member of the protein arginine methyltransferase family, which plays an important role in various tumours. Our study showed that PRMT5 was overexpressed in retinoblastoma and played an important role in retinoblastoma cell growth. EPZ015666 is a novel PRMT5 inhibitor, and we found that it inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. At the same time, EPZ015666 regulated cell cycle related protein (P53, P21, P27, CDK2) expression. In brief, our study showed that PRMT5 promoted retinoblastoma growth, the PRMT5 inhibitor EPZ015666 inhibited retinoblastoma in vitro by regulating P53-P21/P27-CDK2 signaling pathways and slowed retinoblastoma growth in a xenograft model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exer.2020.108286 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phase Ib study of PRT543, an oral protein arginine methyltransferase 5 (PRMT5) inhibitor, in patients with advanced splicing factor-mutant myeloid malignancies.
Leukemia
January 2025
Department of Medicine; Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Article Synopsis
- This study focuses on PRT543, a new oral medication designed to inhibit PRMT5, an enzyme implicated in the growth of certain blood cancers.
- It specifically investigates the effects of PRT543 in patients suffering from advanced myeloid malignancies that have mutations in splicing factors, which are crucial for proper gene expression and can contribute to cancer progression.
- The early Phase Ib trial aims to assess the safety, tolerability, and initial effectiveness of PRT543 in these patients, providing groundwork for potential future treatments.
Discovery of PRMT5 N-Terminal TIM Barrel Ligands from Machine-Learning-Based Virtual Screening.
ACS Omega
January 2025
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.
Protein arginine methyltransferase 5 (PRMT5), which symmetrically dimethylates cytosolic and nuclear proteins, has been demonstrated as an important cancer therapeutic target. In recent years, many advanced achievements in PRMT5 inhibitor development have been made. Most PRMT5 inhibitors in the clinical trial focus on targeting the C-terminal catalytic domain, whereas developing small molecules to interrupt the PRMT5/pICLn (methylosome subunit) protein-protein interface is also of great importance for inhibiting PRMT5.
View Article and Find Full Text PDFBiomedical Effects of Protein Arginine Methyltransferase Inhibitors.
J Biol Chem
January 2025
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, United States. Electronic address:
Protein arginine methyltransferases (PRMTs) are enzymes that catalyze the methylation of arginine residues in eukaryotic proteins, playing critical roles in modulating diverse cellular processes. The importance of PRMTs in the incidence and progression of a wide range of diseases, particularly cancers, such as breast, liver, lung, colorectal cancer, lymphoma, leukemia, and acute myeloid leukemia (AML) is increasingly recognized. This underscores the critical need for the development of effective PRMT inhibitors as therapeutic intervention.
View Article and Find Full Text PDFPRMT5 Inhibition Reduces Hyperinflammation in a Murine Model of Secondary Hemophagocytic Lymphohistiocytosis (HLH).
Blood Adv
January 2025
The Ohio State University, Columbus, Ohio, United States.
Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially lethal hyperinflammatory syndrome characterized by pathologic immune activation and excessive production of proinflammatory cytokines leading to tissue damage and multisystem organ failure. There is an urgent need for the discovery of novel targets and development of therapeutic strategies to treat this rare but deadly syndrome. Protein Arginine Methyltransferase 5 (PRMT5) mediates T cell-based inflammatory responses, making it a potential actionable target for the treatment of HLH.
View Article and Find Full Text PDFAn immunohistochemical and molecular genetic study of 60 colorectal carcinoma brain metastases in pursuit of predictive biomarkers for cancer therapy.
Hum Pathol
January 2025
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Colorectal carcinoma brain metastases (n = 60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!