Identification of cathepsin B as a novel target of hypoxia-inducible factor-1-alpha in HepG2 cells
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003 (China)
- Department of Pathology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou (China)
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)
Highlights: • Cathepsin B (CTSB) is a novel target gene of hypoxia-inducible factor-1-alpha (HIF-1α). • CTSB mRNA and protein levels can be up-regulated in a HIF-1α-dependent manner. • CTSB promoter activity can be elevated by the HIF-1α protein. • HIF-1α protein binds the CTSB promoter directly. Hypoxia-inducible factor-1-alpha (HIF-1α) activates the transcription of many genes that code for proteins involved in angiogenesis, glucose metabolism, cell proliferation/survival, and invasion/metastasis. However, the mechanisms between HIF-1 and its downstream target genes are still poorly understood. Our experimental results had shown that nuclear HIF-1α proteins were significantly induced after HepG2 cells treatment with 1% O{sub 2} for 6 h and reached the peak expression level in 24 h. Meanwhile, the results of RT-qPCR and Western-blotting showed that HIF-1α and cathepsin B (CTSB) expressions increased with a similar pattern in response to hypoxia in the HepG2 cells. Additionally, based on bioinformatics analysis, we identified a hypoxia response element in the CTSB promoter, indicating a possible association between HIF-1α and CTSB. Moreover, luciferase assay was performed to reflect the transcriptional activity mediated through the HIF-1α binding HRE within the CTSB promoter. Furthermore, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) revealed a specific HIF-1α binding activity to the CTSB gene promoter. For the first time, we demonstrated that CTSB is a new HIF-1α-target gene. We believe these findings will contribute to the research and development of neoplasm-targeted therapies.
- OSTI ID:
- 23105634
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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