期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 503, 期 2, 页码 1057-1062出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.06.116
关键词
Hypoxia-inducible factor-1-alpha (HIF-1 alpha); Cathepsin B (CTSB); Transcription; Target gene
资金
- National Natural Science Foundation of China [NSFC-81572307, NSFC-81773096]
- Zhejiang Province Natural Science Foundation of China [LY18H160014]
- Chinese traditional medicine Foundation of Zhejiang Province [2017ZA077]
Hypoxia-inducible factor-1-alpha (HIF-1 alpha) 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-1 alpha proteins were significantly induced after HepG2 cells treatment with 1% O-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-1 alpha 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-1 alpha and CTSB. Moreover, luciferase assay was performed to reflect the transcriptional activity mediated through the HIF-1 alpha binding HRE within the CTSB promoter. Furthermore, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) revealed a specific HIF-1 alpha binding activity to the CTSB gene promoter. For the first time, we demonstrated that CTSB is a new HIF-1 alpha-target gene. We believe these findings will contribute to the research and development of neoplasm-targeted therapies. (C) 2018 Elsevier Inc. All rights reserved.
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