GSK3β negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line

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.