Publications by authors named "N B La Thangue"
Background: Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.
Objective: We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC).
Protein arginine methyltransferase 5 (PRMT5) is over-expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high-risk disease and correlates with an amplified Myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis.
View Article and Find Full Text PDFCitrullination and the protein code: crosstalk between post-translational modifications in cancer.
Philos Trans R Soc Lond B Biol Sci
November 2023
Article Synopsis
- Post-translational modifications (PTMs) of proteins, like arginine citrullination, are crucial for regulating gene expression and cell signaling, impacting disease development, especially in cancer.
- Citrullination is driven by enzymes called peptidylarginine deiminases (PADs), which are gaining attention as potential targets for drug development.
- The review focuses on the roles of PADs in cancer, exploring how citrullination interacts with other PTMs and how these interactions influence cellular processes.
Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes.
View Article and Find Full Text PDFArticle Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a low 5-year survival rate, largely due to its heterogeneity and rapid spread.
- Recent studies indicate that the overexpression of Protein arginine methyltransferase 5 (PRMT5) in PDAC is linked to poorer patient prognosis, making it a target for anti-cancer therapy.
- The combination of the PRMT5 inhibitor T1-44 and the TGF-β1 signaling inhibitor Vactosertib has shown enhanced effectiveness by reducing tumor size and improving survival rates, while disrupting pathways related to cancer progression, particularly through the activation of the tumor suppressor Btg2.