GSK3β negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line
GSK3β negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line
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DOI：
10.1016/j.bbrc.2013.12.020
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发表时间：
2014-01-10
影响因子：
3.1
通讯作者：
Yang, Qing-cheng
中科院分区：
文献类型：
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作者：
Cheng, Dong-dong;Zhao, Hai-guang;Yang, Qing-cheng
缺氧诱导因子1α(HIF1α)是一种参与恶性肿瘤生长、侵袭和转移的转录因子。糖原合成酶激酶3β(GSK3β)是一种蛋白激酶，参与多种信号通路，如Wnt和NF-kappa B通路，通过调节转录因子的表达和细胞凋亡来影响肿瘤的进展。最近的研究表明，GSK3β参与了HIF1α的表达。然而，GSK3β对骨肉瘤细胞HIF1α表达的影响仍不清楚。为了更全面地了解GSK3β与HIF1α之间的关系，本研究采用了小RNA干扰技术、Western印迹分析、实时定量聚合酶链式反应分析和荧光素酶活性检测等方法。实验数据表明，抑制GSK3β可以通过增加HIF1αmRNA的稳定性而不是通过影响HIF1α蛋白的稳定性来增加HIF1α蛋白水平及其靶基因的表达，这一过程可能是由核仁介导的。(C)2013 Elsevier Inc.保留所有权利。
Hypoxia-inducible factor 1 alpha (HIF1 alpha) is a transcription factor involved in the growth, invasion and metastasis of malignant tumors. Glycogen synthase kinase 3 beta (GSK3 beta) is a protein kinase involved in a variety of signaling pathways, such as the Wnt and NF-kappa B pathways; this kinase can affect tumor progress through the regulation of transcription factor expression and apoptosis. Recent studies showed that GSK3 beta was involved in the expression of HIF1 alpha. However, the effect of GSK3 beta on HIF1 alpha expression in osteosarcoma cells remains unknown. To understand the relationship between GSK3 beta and HIF1 alpha comprehensively, small RNA interference techniques, Western blot analyses, quantitative real-time PCR analyses and luciferase assays were used in our study. Experimental data revealed that inhibition of GSK3 beta could increase HIF1 alpha protein levels and expression of its target genes by increasing the stability of the HIF1 alpha mRNA, not by affecting the HIF1 alpha protein stability, and that this process could be mediated by nucleolin. (C) 2013 Elsevier Inc. All rights reserved.