Alessandro Allegra1, Vanessa Innao2, Francesca Polito3, Rosaria Oteri4, Angela Alibrandi5, Andrea Gaetano Allegra2, Giacomo Oteri3, Rosa Maria Di Giorgio4, Caterina Musolino2, M'hammed Aguennouz4. 1. Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", Division of Haematology, University of Messina, Messina, Italy. Electronic address: aallegra@unime.it. 2. Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", Division of Haematology, University of Messina, Messina, Italy. 3. Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", Italy. 4. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 5. Department of Economics, Unit of Statistical and Mathematical Sciences, University of Messina, Messina, Italy.
Abstract
OBJECTIVES: Sirtuins comprise seven family elements (SIRT1-7) involved in various cell signalling pathways comprising cancer inhibition and tumorigenesis. The present study aims to evaluate SIRT2 and SIRT3 gene expression and potential redox reactions in patients with multiple myeloma (MM) at onset and its correlation with disease status, extent and presence of organ damage secondary to myeloma. DESIGN & METHODS: Total RNA was extracted from 17 MM patients and 10 controls to assess gene expression using real-time PCR. The NAD+/NADH ratio as well as the levels of glutathione peroxidase (GPx) and hydrogen peroxide (HP) in peripheral blood mononuclear cells (PBMCs) were determined using established biochemical assays. RESULTS: SIRT2 and SIRT3 expression is reduced in MM patients compared to healthy controls. Correlational analysis demonstrated that SIRT2 reduction is associated with advanced clinical stage and with more advanced bone lesions than in the remaining patients. SIRT3 expression is correlated with lytic bone lesions. Biochemical analysis indicated an imbalance of oxidative stress biomarkers with low concentrations of the antioxidant enzyme GPx, low amounts of NAD + and higher concentrations of pro-oxidant enzyme HP in PBMCs of MM patients compared to controls. Moreover, MM patients with bone lesions had lower concentrations of NAD + and GPx in PBMCs than patients without signs of bone disease. In addition, MM patients had higher quantities of intracellular HP than controls. CONCLUSIONS: Our results demonstrate that SIRT2 and SIRT3 are downregulated in MM and that lower concentrations correlate with an advanced stage of disease and redox imbalance. We conclude that SIRT2 and SIRT3 together with oxidative stress biomarkers, may be useful for improved risk stratification of MM patients.
OBJECTIVES: Sirtuins comprise seven family elements (SIRT1-7) involved in various cell signalling pathways comprising cancer inhibition and tumorigenesis. The present study aims to evaluate SIRT2 and SIRT3 gene expression and potential redox reactions in patients with multiple myeloma (MM) at onset and its correlation with disease status, extent and presence of organ damage secondary to myeloma. DESIGN & METHODS: Total RNA was extracted from 17 MMpatients and 10 controls to assess gene expression using real-time PCR. The NAD+/NADH ratio as well as the levels of glutathione peroxidase (GPx) and hydrogen peroxide (HP) in peripheral blood mononuclear cells (PBMCs) were determined using established biochemical assays. RESULTS:SIRT2 and SIRT3 expression is reduced in MMpatients compared to healthy controls. Correlational analysis demonstrated that SIRT2 reduction is associated with advanced clinical stage and with more advanced bone lesions than in the remaining patients. SIRT3 expression is correlated with lytic bone lesions. Biochemical analysis indicated an imbalance of oxidative stress biomarkers with low concentrations of the antioxidant enzyme GPx, low amounts of NAD + and higher concentrations of pro-oxidant enzyme HP in PBMCs of MMpatients compared to controls. Moreover, MMpatients with bone lesions had lower concentrations of NAD + and GPx in PBMCs than patients without signs of bone disease. In addition, MMpatients had higher quantities of intracellular HP than controls. CONCLUSIONS: Our results demonstrate that SIRT2 and SIRT3 are downregulated in MM and that lower concentrations correlate with an advanced stage of disease and redox imbalance. We conclude that SIRT2 and SIRT3 together with oxidative stress biomarkers, may be useful for improved risk stratification of MMpatients.
Authors: João Vitor Caetano Goes; Luiz Gustavo Carvalho; Roberta Taiane Germano de Oliveira; Mayara Magna de Lima Melo; Lázaro Antônio Campanha Novaes; Daniel Antunes Moreno; Paola Gyuliane Gonçalves; Carlos Victor Montefusco-Pereira; Ronald Feitosa Pinheiro; Howard Lopes Ribeiro Junior Journal: Cancers (Basel) Date: 2022-09-23 Impact factor: 6.575