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RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines

Osteosarcoma (OS) is a pediatric malignant bone tumor with unsatisfying improvements in survival rates due to limited understanding of OS biology and potentially druggable targets. The present study aims to better characterize osteosarcoma U-2 OS, SaOS-2, and MG-63 cell lines that are commonly used...

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Detalles Bibliográficos
Autores principales: Betlej, Gabriela, Ząbek, Tomasz, Lewińska, Anna, Błoniarz, Dominika, Rzeszutek, Iwona, Wnuk, Maciej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356272/
https://www.ncbi.nlm.nih.gov/pubmed/35942470
http://dx.doi.org/10.1016/j.jbo.2022.100448
Descripción
Sumario:Osteosarcoma (OS) is a pediatric malignant bone tumor with unsatisfying improvements in survival rates due to limited understanding of OS biology and potentially druggable targets. The present study aims to better characterize osteosarcoma U-2 OS, SaOS-2, and MG-63 cell lines that are commonly used as in vitro models of OS. We focused on evaluating the differences in cell death pathways, redox equilibrium, the activity of proliferation-related signaling pathways, DNA damage response, telomere maintenance, DNMT2/TRDMT1-based responses and RNA 5-methylcytosine status. SaOS-2 cells were characterized by higher levels of superoxide and nitric oxide that promoted AKT and ERK1/2 activation thus modulating cell death pathways. OS cell lines also differed in the levels and localization of DNA repair regulator DNMT2/TRDMT1. SaOS-2 cells possessed the lowest levels of total, cytoplasmic and nuclear DNMT2/TRDMT1, whereas in MG-63 cells, the highest levels of nuclear DNMT2/TRDMT1 were associated with the most pronounced status of RNA 5-methylcytosine. In silico analysis revealed potential phosphorylation sites at DNMT2/TRDMT1 that may be related to the regulation of DNMT2/TRDMT1 localization. We postulate that redox homeostasis, proliferation-related pathways and DNMT2/TRDMT1-based effects can be modulated as a part of anti-osteosarcoma strategy reflecting diverse phenotypic features of OS cells.