Inhibiting Arginine Methylation as a Tool to Investigate Cross-Talk with Methylation and Acetylation Post-Translational Modifications in a Glioblastoma Cell Line.
Sabrina Francesca SamuelAlistair James MarsdenSrihari DeepakFrancisco RiveroJohn GreenmanPedro Beltran-AlvarezPublished in: Proteomes (2018)
Glioblastomas (GBM) are the most common grade 4 brain tumours; patients have very poor prognosis with an average survival of 15 months after diagnosis. Novel research lines have begun to explore aberrant protein arginine methylation (ArgMe) as a possible therapeutic target in GBM and ArgMe inhibitors are currently in clinical trials. Enzymes known as protein arginine methyltransferases (PRMT1-9) can lead to mono- or di-ArgMe, and in the latter case symmetric or asymmetric dimethylation (SDMA and ADMA, respectively). Using the most common GBM cell line, we have profiled the expression of PRMTs, used ArgMe inhibitors as tools to investigate post-translational modifications cross-talk and measured the effect of ArgMe inhibitors on cell viability. We have identified novel SDMA events upon inhibition of ADMA in GBM cells and spheroids. We have observed cross-talk between ADMA and lysine acetylation in GBM cells and platelets. Treatment of GBM cells with furamidine, a PRMT1 inhibitor, reduces cell viability in 2D and 3D models. These data provide new molecular understanding of a disease with unmet clinical needs.
Keyphrases
- poor prognosis
- induced apoptosis
- cell cycle arrest
- nitric oxide
- long non coding rna
- dna methylation
- amino acid
- signaling pathway
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- genome wide
- gene expression
- multiple sclerosis
- cell death
- escherichia coli
- protein protein
- big data
- staphylococcus aureus
- patient reported
- blood brain barrier
- histone deacetylase
- pseudomonas aeruginosa
- single molecule
- patient reported outcomes
- data analysis
- artificial intelligence
- smoking cessation
- red blood cell
- biofilm formation
- cerebral ischemia