1. UHRF1 promotes aerobic glycolysis and proliferation via suppression of SIRT4 in pancreatic cancer.
- Author
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Hu Q, Qin Y, Ji S, Xu W, Liu W, Sun Q, Zhang Z, Liu M, Ni Q, Yu X, and Xu X
- Subjects
- Apoptosis physiology, CCAAT-Enhancer-Binding Proteins genetics, Cell Line, Tumor, Cell Proliferation physiology, Glycolysis genetics, Humans, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Neoplasm Metastasis pathology, Oxygen Consumption physiology, Ubiquitin-Protein Ligases genetics, CCAAT-Enhancer-Binding Proteins metabolism, Glycolysis physiology, Mitochondrial Proteins antagonists & inhibitors, Pancreatic Neoplasms pathology, Sirtuins antagonists & inhibitors, Ubiquitin-Protein Ligases metabolism
- Abstract
UHRF1 (ubiquitin like with plant homeodomain and ring finger domains 1) is an epigenetic modifier that is overexpressed in some cancers, including pancreatic cancer, and mediates silencing of tumor suppressor genes. However, the role of UHRF1 in regulating pancreatic cancer metabolism and metastasis is not clear. In the present study, we demonstrated that silencing UHRF1 significantly inhibited aerobic glycolysis in pancreatic cancer cells. Furthermore, we demonstrated that UHRF1 knockdown decreased hypoxia inducible factor (HIF)1α levels and HIF1α targeted glycolytic genes. The Cancer Genome Atlas dataset analysis supported this observation. The Sirtuin (SIRT) family members regulate aerobic glycolysis in many cancers. We analyzed the correlation between UHRF1 and SIRT3-5 expression and found a significant negative correlation between UHRF1 and SIRT4. Further transcriptional and functional analysis demonstrates that SIRT4 is a downstream target of UHRF1 and negatively regulated aerobic glycolysis, cell proliferation and tumor growth. Our study identified a novel UHRF1/SIRT4 axis in regulation of pancreatic cancer cell proliferation, metabolism, and metastasis., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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