Jesionek-Kupnicka Dorota, Braun Marcin, Trąbska-Kluch Berenika, Czech Joanna, Szybka Małgorzata, Szymańska Bożena, Kulczycka-Wojdala Dominika, Bieńkowski Michał, Kordek Radzisław, Zawlik Izabela
Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.
Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
Arch Med Sci. 2019 Mar;15(2):504-512. doi: 10.5114/aoms.2017.69374. Epub 2017 Jul 31.
and alterations play a crucial role in glioblastoma (GB) pathogenesis. and function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting and functionality.
In 49 GB patients, we analyzed the possible associations between and its miRNA regulators , , and , as well as and its miRNA regulators and . We evaluated the possible influence of mutational and methylation status on the pre-identified associations.
In patients with immunohistochemistry-detected overexpression, expression levels of and were negatively correlated ( = -0.56, = 0.0195), and in patients with mutations, expression levels of and were negatively correlated ( = -0.67, = 0.0330). In patients with methylation, expression levels of were negatively correlated with and expression levels ( = -0.61, = 0.0269 and = -0.34, = 0.0727, respectively).
Our findings demonstrate that selected miRNAs are significantly correlated with and levels, but the extent of this correlation differs regarding the and mutational and promoter methylation status.
[基因名称1]和[基因名称2]的改变在胶质母细胞瘤(GB)发病机制中起关键作用。[基因名称1]和[基因名称2]的功能受多种病理机制影响,如点突变或启动子甲基化,这些已得到充分表征。这两个基因的表达也可受其他机制调控,例如微小RNA(miRNA)。此外,各种病理过程之间可能发生相互作用,进一步影响[基因名称1]和[基因名称2]的功能。
在49例GB患者中,我们分析了[基因名称1]与其miRNA调节因子[miRNA名称1]、[miRNA名称2]和[miRNA名称3]之间以及[基因名称2]与其miRNA调节因子[miRNA名称4]和[miRNA名称5]之间的可能关联。我们评估了突变和甲基化状态对预先确定的关联的可能影响。
在免疫组化检测到[基因名称1]过表达的患者中,[基因名称2]和[miRNA名称6]的表达水平呈负相关(r = -0.56,P = 0.0195),在有[基因名称1]突变的患者中,[基因名称2]和[miRNA名称7]的表达水平呈负相关(r = -0.67,P = 0.0330)。在有[基因名称2]甲基化的患者中,[基因名称2]的表达水平与[基因名称1]和[miRNA名称8]的表达水平呈负相关(分别为r = -0.61,P = 0.0269和r = -0.34,P = 0.0727)。
我们的研究结果表明,所选miRNA与[基因名称1]和[基因名称2]水平显著相关,但这种相关性的程度因[基因名称1]和[基因名称2]的突变及启动子甲基化状态而异。