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RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines
Journal of Bone Oncology ( IF 3.1 ) Pub Date : 2022-07-30 , DOI: 10.1016/j.jbo.2022.100448
Gabriela Betlej 1 , Tomasz Ząbek 2 , Anna Lewińska 3 , Dominika Błoniarz 3 , Iwona Rzeszutek 3 , Maciej Wnuk 3
Affiliation  

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.



中文翻译:

RNA 5-甲基胞嘧啶状态与骨肉瘤细胞系中的 DNMT2/TRDMT1 核定位有关

骨肉瘤 (OS) 是一种儿科恶性骨肿瘤,由于对 OS 生物学和潜在药物靶点的了解有限,其存活率的提高并不令人满意。本研究旨在更好地表征通常用作体外的骨肉瘤 U-2 OS、SaOS-2 和 MG-63 细胞系操作系统的模型。我们专注于评估细胞死亡途径、氧化还原平衡、增殖相关信号通路的活性、DNA 损伤反应、端粒维持、基于 DNMT2/TRDMT1 的反应和 RNA 5-甲基胞嘧啶状态的差异。SaOS-2 细胞的特点是更高水平的超氧化物和一氧化氮促进 AKT 和 ERK1/2 活化,从而调节细胞死亡途径。OS 细胞系在 DNA 修复调节因子 DNMT2/TRDMT1 的水平和定位方面也存在差异。SaOS-2 细胞具有最低水平的总、细胞质和核 DNMT2/TRDMT1,而在 MG-63 细胞中,最高水平的核 DNMT2/TRDMT1 与 RNA 5-甲基胞嘧啶的最显着状态相关。计算机分析揭示了 DNMT2/TRDMT1 的潜在磷酸化位点,这可能与 DNMT2/TRDMT1 定位的调节有关。我们假设氧化还原稳态、增殖相关途径和基于 DNMT2/TRDMT1 的效应可以作为反映 OS 细胞不同表型特征的抗骨肉瘤策略的一部分进行调节。

更新日期:2022-08-03
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