Up-regulation of micro-RNA-221 (miRNA-221; chr Xp11.3) and caspase-3 accompanies down-regulation of the survivin-1 homolog BIRC1 (NAIP) in glioblastoma multiforme (GBM)

Up-regulation of micro-RNA-221 (miRNA-221; chr Xp11.3) and caspase-3 accompanies down-regulation of the survivin-1 homolog BIRC1 (NAIP) in glioblastoma multiforme (GBM)
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DOI:
10.1007/s11060-008-9688-0
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发表时间:
2009-01-01
影响因子:
3.9
通讯作者:
Culicchia, F.
Culicchia, F.
中科院分区:
医学2区
文献类型:
--
作者:
Lukiw, W. J.;Cui, J. G.;Culicchia, F.

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多形性胶质母细胞瘤(GBM)是一类快速增殖、侵袭和破坏周围脑组织的恶性胶质瘤。本研究检测了6个ATCC胶质瘤和GBM细胞系以及从人脑活检获得的14个胶质瘤和GBM样本中的microRNA(MiRNA)形态和miRNA对基因表达的影响。我们观察到miRNA-221的选择性上调和编码Survivin-1同源基因BIRC1的miRNA-221信使RNA靶标的下调,后者是神经元凋亡抑制蛋白(NIAP)和神经变性的标志。BIRC5(Survivin-1)和caspase-3的表达显著上调,尤其是在IV期GBM中。这些研究表明,BIRC家族的神经细胞命运调节因子的丰度和形态在胶质瘤和GBM中受到不同的调控,可能有助于细胞凋亡信号的渐进性变化和神经细胞周期功能的改变。
Glioblastoma multiforme (GBM) represents a class of malignant gliomas which rapidly proliferate, invade and destroy surrounding brain tissues. This study examined micro-RNA (miRNA) speciation and miRNA effects on gene expression in six ATCC glioma and GBM cell lines and in 14 glioma and GBM samples obtained from human brain biopsy. We observed selective up-regulation of miRNA-221 and down-regulation of a miRNA-221 messenger RNA target encoding the survivin-1 homolog BIRC1, a neuronal inhibitor of apoptosis protein (NIAP) and marker for neurodegeneration. The expression of BIRC5 (survivin-1) and caspase-3 were found to be significantly up-regulated, particularly in stage IV GBM. These studies suggest that the abundance and speciation of the BIRC family of neural cell fate regulators are differentially regulated in glioma and GBM, and may contribute to progressive changes in apoptotic signaling and altered neural cell cycling functions.