High nuclear expression of protein arginine methyltransferase-5 is a potentially useful marker to estimate submucosal invasion in endoscopically resected early colorectal carcinoma

2015 ◽  
Vol 65 (10) ◽  
pp. 541-548 ◽  
Author(s):  
Min Gyoung Pak ◽  
Hyoun Wook Lee ◽  
Mee Sook Roh
Keyword(s):  
Colorectal Carcinoma ◽  
Submucosal Invasion ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Nuclear Expression ◽  
Early Colorectal Carcinoma ◽  
Protein Arginine Methyltransferase 5

scholarly journals Transcriptional perturbation of protein arginine methyltransferase-5 exhibits MTAP-selective oncosuppression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Busacca ◽  
Qi Zhang ◽  
Annabel Sharkey ◽  
Alan G. Dawson ◽  
David A. Moore ◽  
...  
Keyword(s):  
Small Molecule ◽  
Selective Vulnerability ◽  
Dependent Manner ◽  
Histone H4 ◽  
Wild Type ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Methylthioadenosine Phosphorylase ◽  
Protein Arginine Methyltransferase 5

AbstractWe hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.

scholarly journals Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors

2019 ◽  
Vol 10 (7) ◽  
pp. 1033-1038 ◽  
Author(s):  
Hong Lin ◽  
Min Wang ◽  
Yang W. Zhang ◽  
Shuilong Tong ◽  
Raul A. Leal ◽  
...  
Keyword(s):  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Protein Arginine Methyltransferase 5

scholarly journals SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth

2017 ◽  
Vol 128 (1) ◽  
pp. 517-530 ◽  
Author(s):  
Hironari Tamiya ◽  
Hyungsoo Kim ◽  
Oleksiy Klymenko ◽  
Heejung Kim ◽  
Yongmei Feng ◽  
...  
Keyword(s):  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Melanoma Growth ◽  
Protein Arginine Methyltransferase 5

scholarly journals Protein arginine methyltransferase 5: A novel therapeutic target for triple‐negative breast cancers

2019 ◽  
Vol 8 (5) ◽  
pp. 2414-2428 ◽  
Author(s):  
Mathilde Vinet ◽  
Samyuktha Suresh ◽  
Virginie Maire ◽  
Clarisse Monchecourt ◽  
Fariba Némati ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Triple Negative ◽  
Breast Cancers ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Novel Therapeutic ◽  
Protein Arginine Methyltransferase 5
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