title: GSK3β negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line.
abstract: Hypoxia-inducible factor 1α (HIF1α) is a transcription factor involved in the growth, invasion and metastasis of malignant tumors. Glycogen synthase kinase 3 beta (GSK3β) is a protein kinase involved in a variety of signaling pathways, such as the Wnt and NF-κB pathways; this kinase can affect tumor progress through the regulation of transcription factor expression and apoptosis. Recent studies showed that GSK3β was involved in the expression of HIF1α. However, the effect of GSK3β on HIF1α expression in osteosarcoma cells remains unknown. To understand the relationship between GSK3β and HIF1α 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 GSK3β could increase HIF1α protein levels and expression of its target genes by increasing the stability of the HIF1α mRNA, not by affecting the HIF1α protein stability, and that this process could be mediated by nucleolin.
authors: Department of Orthopeadics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors: Dong-dong
authors: DD
authors: Cheng
authors: Department of Vascular Surgery, Shanghai Jiao Tong University Affiliated Ninth People's Hospital, Shanghai 200011, China.
authors: Hai-guang
authors: HG
authors: Zhao
authors: Huazhong University of Science and Technology, Wuhan 430074, China.
authors: Yun-song
authors: YS
authors: Yang
authors: Department of Orthopeadics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors: Tu
authors: T
authors: Hu
authors: Department of Orthopeadics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: tjyqc@163.com.
authors: Qing-cheng
authors: QC
authors: Yang
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C497442:HIF1A protein, human
keywords: ARNT; Chx; EPO; GLUT1; GSK3β; HIF1α; Nucleolin; ODD; Osteosarcoma; SDS–PAGE; VEGF; VHL; aryl hydrocarbon receptor nuclear translocator; cycloheximide; erythropoietin; glucose transporter 1; glycogen synthase kinase 3 beta; hypoxia-inducible factor 1α; mRNA; oxygen-dependent degradation; siRNA; small interfering RNA; sodium dodecyl sulfate polyacrylamide gel electrophoresis; vascular endothelial growth factor; von Hippel-Lindau