Biology subjects

Marina, D.

Publications and source records attributed to Marina, D..

2 recordsLinked to original sources

bioRxiv2024

Chemotherapy causes a reversible decrease in VMP1/MIR21 DNA methylation in granulocytes from breast cancer survivors

BackgroundDNA methylation alterations within the VMP1/MIR21 gene region, a potential epigenetic biomarker of systemic inflammation, have been demonstrated in mononuclear blood cells from early breast cancer (BC) patients after chemotherapy. Whether these changes are present in granulocytes, persist in the years after treatment, and affect VMP1 or MIR21 gene expression, remains unknown. AimWe aimed to investigate whether adjuvant chemotherapy alters the DNA methylation and gene expression of VMP1/MIR21 in granulocytes from postmenopausal BC patients and, if so, whether these treatment-induced changes are reversible in the first two years after completed chemotherapy. MethodsWhole blood samples were obtained from 30 postmenopausal BC patients before chemotherapy and every six months for two years, and from 10 healthy age- and BMI-matched controls. DNA and RNA was extracted from isolated granulocytes, and DNA methylation of four CpG sites located in the gene body of VMP1, which is situated in the promoter region of MIR21, was assessed through bisulfite pyrosequencing. qPCR was used for assessment of VMP1 and MIR21 expression. ResultsVMP1/MIR21 was significantly demethylated in granulocytes from BC patients shortly after completed chemotherapy compared to before (10 percentage points decrease, p<0.0001). Six months thereafter, DNA methylation values were significantly increased (6 percentage points, p = 0.002), and they were further increased to pre-chemotherapy levels 12, 18 and 24 months post chemotherapy. Chemotherapy did not cause significant changes in the expression of VMP1 or MIR21. ConclusionThe unique follow-up samples in this study demonstrated that chemotherapy induced a transient reduction in DNA methylation of the VMP1/MIR21 region in granulocytes from postmenopausal BC patients. Although transient, chemotherapy-induced epigenetic changes in blood cells may contribute to the increased risk of inflammatory-related comorbidities in BC survivors.

molecular biology↗

bioRxiv2022

Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer

BackgroundAdjuvant chemo- and radiotherapy cause cellular damage not only to cancerous but also to healthy dividing cells. Antineoplastic treatments have been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on circulating human peripheral blood mononuclear cells (PBMCs) remain unknown. AimWe aimed to identify changes in mitochondrial respiration of PBMCs after adjuvant chemo- and radiotherapy in postmenopausal early breast cancer (EBC) patients and relate these to metabolic parameters of the patients. MethodsTwenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy treatment often administered in combination with radiotherapy (n=18). Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics were furthermore assessed. ResultsRespiration of intact and permeabilized PBMCs from EBC patients was significantly increased after adjuvant chemo- and radiotherapy (p=6x10-5 and p=1x10-7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17-43% compared to before therapy commencement. Leukocyte counts (p=1x10-4), hemoglobin levels (p=0.0003), and HDL cholesterol (p=0.003) decreased while triglyceride (p=0.01) and LDL levels (p=0.02) increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters correlated significantly with PBMC respiration. ConclusionThis study shows that mitochondrial respiration in circulating PBMCs is significantly increased after adjuvant chemo- and radiotherapy in postmenopausal EBC patients. The increase might be explained by a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation rather than glycolysis or a generally increased mitochondrial content in PBMCs. Both parameters might be influenced by therapy-induced changes to the bone marrow or vascular microenvironment wherein PBMCs differentiate and reside.

cell biology↗