All India Institute of Medical Sciences, New Delhi, 110029, India.
National Brain Research Centre, Nainwal Mode, NH-8, Manesar, Gurgaon, Haryana, 122051, India.
J Mol Med (Berl). 2017 Nov;95(11):1215-1226. doi: 10.1007/s00109-017-1571-z. Epub 2017 Aug 25.
Gangliogliomas (GGs) are the most commonly diagnosed long-term epilepsy-associated tumors (LEATs). Although molecular characterizations of brain tumors have identified few novel biomarkers among the LEATs, mechanisms of pathogenesis remain poorly understood. In this study, global microarray-based microRNA (miRNA) expression profile on a set of 9 GGs indicated 66 miRNAs to be differentially expressed in GG as compared to normal brain. The differences validated by qRT-PCR indicated microRNA-217 to be the most downregulated. Through insilico analysis, ERK1/2 and casein kinase (CK-2α) were predicted to be miR-217 regulated. As decreased miR-217 expression was concomitant with upregulated ERK1/2 and CK-2α levels in GG; the interplay between these molecules was investigated in primary human neural precursor cells to mimic the glioneuronal characteristics of these tumors. miR-217 over-expression-mediated decrease in pERK, CK-2α, and mGluR1 levels was accompanied with increase in glycogen accumulation. Importantly, increase in miR-217 levels upon CK-2α inhibition indicated inverse correlation between the two. Inhibition of CK-2α also decreased ERK and mGluR1 levels. By demonstrating, for the first time, the existence of miR-217-CK-2 cross talk and its effects on known epileptogenic factors, these findings provide a unique insight into the pathogenesis of ganglioglioma. By highlighting the role of CK-2 in affecting miR-217/ERK/mGluR1 interplay, this study suggests that targeting CK-2 may afford a novel strategy aimed at LEATs.
Global microarray of ganglioglioma indicates downregulation of miR-217. Decreased miR-217 expression is concomitant with elevated CK-2α and Erk levels. Inverse correlation between miR-217 and CK-2α in primary human neural precursors. miR-217 agomir or CK-2α inhibition decreases pERK and mGluR1 levels. CK-2α affects miR-217/ERK/mGluR1 interplay in long-term epilepsy-associated tumors.
神经节神经胶质瘤（GGs）是最常见的诊断为长期癫痫相关肿瘤（LEATs）。尽管脑肿瘤的分子特征在 LEATs 中确定了一些新的生物标志物，但发病机制仍知之甚少。在这项研究中，一组 9 个 GG 的基于微阵列的 miRNA（miRNA）的全基因组表达谱表明，与正常脑相比，66 个 miRNA 在 GG 中表达差异。通过 qRT-PCR 验证的差异表明，miR-217 是下调最明显的。通过计算机分析，预测 ERK1/2 和酪蛋白激酶（CK-2α）是 miR-217 调节的。由于在 GG 中，miR-217 表达的降低与 ERK1/2 和 CK-2α 水平的上调同时发生；因此在原代人神经前体细胞中研究这些分子之间的相互作用，以模拟这些肿瘤的神经胶质特性。miR-217 过表达介导的 pERK、CK-2α 和 mGluR1 水平降低伴随着糖原积累的增加。重要的是，CK-2α 抑制后 miR-217 水平的增加表明两者之间存在反比关系。CK-2α 的抑制也降低了 ERK 和 mGluR1 的水平。通过首次证明 miR-217-CK-2 交叉对话的存在及其对已知致痫因子的影响，这些发现为神经节神经胶质瘤的发病机制提供了独特的见解。通过强调 CK-2 在影响 miR-217/ERK/mGluR1 相互作用中的作用，本研究表明，针对 CK-2 可能提供一种针对 LEATs 的新策略。
神经节神经胶质瘤的全基因组微阵列表明 miR-217 的下调。miR-217 表达降低与 CK-2α 和 Erk 水平升高同时发生。在原代人神经前体细胞中，miR-217 和 CK-2α 之间存在反比关系。miR-217 激动剂或 CK-2α 抑制降低 pERK 和 mGluR1 水平。CK-2α 影响长期癫痫相关肿瘤中的 miR-217/ERK/mGluR1 相互作用。
