Differential expression and clinical significance of three inflammation-related microRNAs in gangliogliomas.

Differential expression and clinical significance of three inflammation-related microRNAs in gangliogliomas.
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DOI:
10.1186/s12974-015-0315-7
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发表时间:
2015-05-20
影响因子:
9.3
通讯作者:
Aronica E
Aronica E
中科院分区:
医学1区
文献类型:
--
作者:
Prabowo AS;van Scheppingen J;Iyer AM;Anink JJ;Spliet WG;van Rijen PC;Schouten-van Meeteren AY;Aronica E

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miR 21、miR 146和miR 155代表了三种microRNA,它们已被证明在免疫和炎症反应的调节中发挥关键作用。在本研究中,我们研究了这三种miRNA在胶质神经元肿瘤(神经节细胞胶质瘤,GG)中的差异表达和临床意义,这些肿瘤的特征是先天免疫反应的显著激活。采用Taqman PCR检测34例GG中miR 21、miR 146和miR 155的表达水平,其中包括15例有足够量的病灶周围皮质的病例。它们的表达与肿瘤的特征和癫痫的临床病史有关。此外,原位杂交用于评估它们在肿瘤和瘤周皮质中的细胞分布。与对照样品相比,在肿瘤和肿瘤周围皮质中观察到miR 146 a的表达增加。在神经元和星形胶质细胞中均检测到miR 146 a。肿瘤和瘤周miR 146 a表达与癫痫发作频率和活化小胶质细胞密度呈负相关。观察到miR 21和miR 155的神经元和星形胶质细胞表达,肿瘤内miR 21的表达增加,肿瘤周围区域中miR 155的表达增加。在肿瘤的星形胶质细胞成分中,观察到miRNA水平与推定靶点表达之间的负相关性。我们报告了三种已知与炎症相关的miRNA在GG患者的肿瘤和瘤周皮质中的差异调节。此外,我们的研究结果表明,miR 146 a的表达和癫痫之间的功能关系,无论是直接在癫痫发生或癫痫发作活动的调制。本文的在线版本(doi:10.1186/s12974-015-0315-7)包含补充材料,可供授权用户使用。
miR21, miR146, and miR155 represent a trio of microRNAs which has been shown to play a key role in the regulation of immune and inflammatory responses. In the present study, we investigated the differential expression and clinical significance of these three miRNAs in glioneuronal tumors (gangliogliomas, GGs) which are characterized by prominent activation of the innate immune response. The expression levels of miR21, miR146, and miR155 were evaluated using Taqman PCR in 34 GGs, including 15 cases with sufficient amount of perilesional cortex. Their expression was correlated with the tumor features and the clinical history of epilepsy. In addition, in situ hybridization was used to evaluate their cellular distribution in both tumor and peritumoral cortex. Increased expression of miR146a was observed in both tumor and peritumoral cortex compared to control samples. miR146a was detected in both neuronal and astroglial cells. Tumor and peritumoral miR146a expression was negatively correlated with frequency of seizures and the density of activated microglial cells. Neuronal and astroglial expression was observed for both miR21 and miR155 with increased expression of miR21 within the tumor and miR155 in the peritumoral region. Negative correlations were observed between the miRNA levels and the expression of putative targets within the astroglial component of the tumor. We report a differential regulation of three miRNAs, known to be related to inflammation, in both tumor and peritumoral cortex of patients with GG. Moreover, our findings suggest a functional relationship between miR146a expression and epilepsy, either directly in epileptogenesis or as modulation of seizure activity. The online version of this article (doi:10.1186/s12974-015-0315-7) contains supplementary material, which is available to authorized users.
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发表时间: 2005-06-01
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通讯作者: Troost, D
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发表时间: 2003-06-01
期刊: EPILEPSIA
影响因子: 5.6
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