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Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma

机译:stathmin参与胶质母细胞瘤母体的胚胎亮氨酸拉链激酶途径

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Background Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in cell cycle, differentiation, proliferation, and apoptosis. These multiple features are consistent with it being a potential anticancer target. Nevertheless, the MELK pathway in tumorigenesis is not yet completely understood. This study aims to identify proteins associated with MELK pathway in astrocytomas. To this end, proteomic data of the human glioma cell line U87MG transfected with siRNA for MELK were compared with non-target transfected control cells and compared with oligonucleotide microarray data. Results In both assays, we identified stathmin/oncoprotein 18 (STMN1), involved in cell cycle. STMN1 gene expression was further assessed in a series of 154 astrocytomas and 22 non-neoplastic brain samples by qRT-PCR. STMN1 expression was significantly increased in malignant diffusely infiltrative astrocytomas compared with pilocytic astrocytoma ( p ?0.0001). A strong correlation between MELK and STMN1 expressions was observed ( r =?0.741, p ?0.0001) in glioblastoma (GBM) samples. However, no difference on survival times was found when compared GBM cases with upregulated and downregulated STMN1 ( Breslow =?0.092, median survival time: 11 and 13?months, respectively). Functional assays knocking down MELK by siRNA in GBM cell line showed that gene and protein expression of both MELK and stathmin were diminished. On the other hand, when the same analysis was performed for STMN1 , only stathmin gene and protein was silenced. Conclusions The results presented herein point stahtmin as a downstream target in the MELK pathway that plays a role in malignant progression of astrocytomas.
机译:背景技术孕妇胚胎亮氨酸拉链激酶(MELK)是一种丝氨酸/苏氨酸激酶,参与细胞周期,分化,增殖和凋亡。这些多重特征与它作为潜在的抗癌靶标是一致的。然而,尚未完全理解肿瘤发生中的MELK途径。本研究旨在鉴定与星形细胞瘤中MELK途径相关的蛋白质。为此,将针对siRNA转染MELK的人神经胶质瘤细胞系U87MG的蛋白质组学数据与非靶转染对照细胞进行了比较,并与寡核苷酸微阵列数据进行了比较。结果在两种测定中,我们都鉴定出了与细胞周期有关的stathmin /癌蛋白18(STMN1)。通过qRT-PCR在一系列154个星形细胞瘤和22个非肿瘤性脑样本中进一步评估了STMN1基因的表达。与恶性弥漫性浸润性星形细胞瘤相比,STMN1表达显着增加(p <?0.0001)。在胶质母细胞瘤(GBM)样品中观察到MELK和STMN1表达之间有很强的相关性(r =?0.741,p <?0.0001)。但是,与GBMN病例的STMN1上调和下调相比,生存时间没有差异(Breslow = 0.092,中位生存时间分别为11和13个月)。在GBM细胞系中通过siRNA敲低MELK的功能分析表明,MELK和stathmin的基因和蛋白质表达均降低。另一方面,当对STMN1进行相同的分析时,仅使stathmin基因和蛋白质沉默。结论本文给出的结果表明,stahtmin作为MELK途径的下游靶标,在星形细胞瘤的恶性进展中起作用。

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