Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS.
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http://dx.doi.org/10.18632/oncotarget.12688 | DOI Listing |
Adv Biomed Res
November 2024
Department of Cellular and Molecular Nutrition, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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View Article and Find Full Text PDFCancer Cell Int
December 2024
Department of Biology, University of Alabama at Birmingham, 3100 East Science Hall, 902 14th Street South, Birmingham, AL, 35294-1170, USA.
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View Article and Find Full Text PDFCommun Biol
December 2024
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University; State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China.
Inevitable gefitinib resistance is the biggest bottleneck in current treatment and the mechanisms are not fully understood. Here, we observe that PFTK1 (also named CDK14) is significantly enhanced in NSCLC with gefitinib resistance. And the upregulation of PFTK1 is negatively associated with progression-free survival (PFS) in NSCLC patients who receive gefitinib treatment.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Unité Organisation Nucléaire et Oncogenèse, INSERM U993, Institut Pasteur, Université Paris Cité, 75015 Paris, France.
Hepatoblastoma is the most common primary liver malignancy in children, with metabolic reprogramming playing a critical role in its progression due to the liver's intrinsic metabolic functions. Enhanced glycolysis, glutaminolysis, and fatty acid synthesis have been implicated in hepatoblastoma cell proliferation and survival. In this study, we screened for altered overexpression of metabolic enzymes in hepatoblastoma tumors at tissue and single-cell levels, establishing and validating a hepatoblastoma tumor expression metabolic score using machine learning.
View Article and Find Full Text PDFBrain Behav Immun
December 2024
Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Building 24-6, Denmark. Electronic address:
Poor sleep quality is a major issue for many adolescents and is associated with fatigue, poor academic performance, and depression. Adolescence is a crucial neurodevelopmental stage where multiple neuropsychiatric illnesses often emerge, suggesting increased central nervous system vulnerability, specifically at this age, which could be exacerbated by poor sleep. Studies on adolescent mice show that sleep deprivation or sleep disturbance (SD) induces structural and functional brain changes, indicating that SD affects the adolescent brain.
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