Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic progression to identify a new molecular target and to provide new therapeutic approach. We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the expression using siRNA. We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than the nuclear localization ( < 0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased from low grade primary tissue to metastatic tissues. The cytoplasmic localization of KMT2C could lead to a change in its function supporting osteosarcoma carcinogenesis and progression. Our hypothesis is that KMT2C could affect the enhancer activity of genes influencing the invasive properties and metastatic potential of osteosarcoma.
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http://dx.doi.org/10.18632/oncotarget.25755 | DOI Listing |
Bone
March 2025
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China. Electronic address:
iScience
December 2024
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
Genetic mutations arising from various internal and external factors drive cells to become cancerous. Cancerous cells undergo numerous changes, including metabolic reprogramming and epigenetic modifications, to support their abnormal proliferation. This metabolic reprogramming leads to the altered expression of many metabolic enzymes and the accumulation of metabolites.
View Article and Find Full Text PDFMethods Mol Biol
July 2024
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA, USA.
Epigenome editing applications are gaining broader use for targeted transcriptional control as more enzymes with diverse chromatin-modifying functions are being incorporated into fusion proteins. Development of these fusion proteins, called epigenome editors, has outpaced the study of proteins that interact with edited chromatin. One type of protein that acts downstream of chromatin editing is the reader-effector, which bridges epigenetic marks with biological effects like gene regulation.
View Article and Find Full Text PDFAtherosclerosis
August 2024
Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia. Electronic address:
Cardiovascular diseases (CVD), including coronary heart disease and stroke, comprise the number one cause of mortality worldwide. A major contributor to CVD is atherosclerosis, which is a low-grade inflammatory disease of vasculature that involves a pathological build-up of plaque within the arterial walls. Studies have shown that regulation of gene expression via transcription factors and epigenetic mechanisms play a fundamental role in transcriptomic changes linked to the development of atherosclerosis.
View Article and Find Full Text PDFCardiovasc Diabetol
April 2024
Cardiology Unit, Department of Medicine-Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Background: Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium.
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