کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1983358 | 1539871 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
R132H mutation in IDH1 gene reduces proliferation, cell survival and invasion of human glioma by downregulating Wnt/β-catenin signaling
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کلمات کلیدی
NF-κBHIF1-αIDH1FBSDABPI3KROS - ROSIsocitrate dehydrogenase 1 - ایزوسیترات دهیدروژناز 1β-catenin - بتا-کاتنینempty vector - بردار خالیProliferation - ترویجInvasion - تهاجمEMT - تکنسین فوریتهای پزشکیdiaminobenzidine - دیامینو بنزیدینWorld Health Organization - سازمان بهداشت جهانیfetal bovine serum - سرم جنین گاوhypoxia-inducible factor 1-α - عامل القایی هیپوکسی 1-αnuclear factor-κB - فاکتور هسته ای κBphosphoinositide 3-kinase - فسفینوزیتید 3-کینازWHO - کهGlioma - گلیوما Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mutations in the isocitrate dehydrogenase 1 (IDH1) gene commonly occur in gliomas. Remarkably, the R132H mutation in IDH1 (IDH1-R132H) is associated with better prognosis and increased survival than patients lacking this mutation. The molecular mechanism underlying this phenomenon is largely unknown. In this study, we investigated potential cross-talk between IDH1-R132H and Wnt/β-catenin signaling in regulating the cellular properties of human glioma. Although aberrant nuclear accumulation of β-catenin is linked to the malignant progression of gliomas, its association with IDH1 remains unknown. We identified an inverse correlation between IDH1-R132H and the expression and activity of β-catenin in human gliomas. In addition, overexpression of IDH1-R132H in glioblastoma cell lines U87 and U251 led to reduced cell proliferation, migration and invasion, accompanied by increased apoptosis. At the molecular level, we detected a significant reduction in the expression, nuclear accumulation and activity of β-catenin following overexpression of IDH1-R132H. A microarray-based comparison of gene expression indicated that several mediators, effectors and targets of Wnt/β-catenin signaling are downregulated, while negative regulators are upregulated in IDH1-R132H gliomas. Further, overexpression of β-catenin in IDH1-R132H glioma cells restored the cellular phenotype induced by this mutation. Specifically, β-catenin abrogated the decrease in proliferation, invasion and migration, and the increase in apoptosis, triggered by overexpression of IDH1-R132H. Finally, we demonstrate that xenografts of IDH1-R132H overexpressing U87 cells can significantly decrease the growth of tumors in vivo. Altogether, our results strongly suggest that the R132H mutation in IDH1 serves a tumor suppressor function in human glioma by negatively regulating Wnt/β-catenin signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 73, April 2016, Pages 72-81
Journal: The International Journal of Biochemistry & Cell Biology - Volume 73, April 2016, Pages 72-81
نویسندگان
Daming Cui, Jie Ren, Jinlong Shi, Lijing Feng, Ke Wang, Tao Zeng, Yi Jin, Liang Gao,