Lipid metabolism reprogramming roles in mantel cell lymphoma growth and survival
نویسندگان
چکیده
Introduction: Metabolic reprogramming is a hallmark of cancer progression. However, there are few studies in mantle cell lymphoma (MCL). Protein arginine methyltransferase 5 (PRMT5), catalyzes monomethylation and symmetric demethylation residues on histone nonhistone proteins participates tumor This study aimed to investigate the mechanism PRMT5-induced lipid MCL. Method: Lymph node, bone marrow biopsy, peripheral blood specimens MCL lines were utilized as models. Liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based analysis was performed measure steady-state level metabolites. GSE93291 dataset immunohistochemistry (IHC) staining determine relationship between expression levels PRMT5 patient outcome. CRISPR/Cas9 editing employed engineer loss-of-function models other key genes involved metabolism. Result: Non-targeted LC-MS/MS showed that metabolites rich (Figure 1A 1B). Through systematic metabolism-related prognosis GSE93291, PRMT5, SREBP1, SRENP2, FASN MYC found be associated with overall survival (OS) patients 1F–1J), which suggested metabolism may development IHC 105 tissues confirmed elevated significantly poor progression free (PFS) (P = 0.039) OS < 0.001) 1D 1E). Multivariate Cox regression high an independent prognostic indicator 0.003). Gene transcriptome sequencing downregulation caused reduced SREBP1/SREBP2 change metabolite 1K). depletion impaired outgrowth increased apoptosis cells. In primary samples, protein correlated 0.001). knockout blocked mRNA expression, suggesting requisite role transcription regulation. Further molecular biological methods used verify could participate through by changing 1L). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic Prognostic Biomarkers, Metabolism No conflicts interests pertinent abstract.
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ژورنال
عنوان ژورنال: Hematological Oncology
سال: 2023
ISSN: ['1099-1069', '0278-0232']
DOI: https://doi.org/10.1002/hon.3164_167