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UHRF1 promotes aerobic glycolysis and proliferation via suppression of SIRT4 in pancreatic cancer
- Source :
- Cancer letters. 452
- Publication Year :
- 2019
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Ubiquitin-Protein Ligases
Apoptosis
Biology
Metastasis
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Oxygen Consumption
Pancreatic cancer
Cell Line, Tumor
medicine
Gene silencing
Humans
Sirtuins
Glycolysis
Neoplasm Metastasis
Cell Proliferation
Cell growth
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Pancreatic Neoplasms
030104 developmental biology
Oncology
Hypoxia-inducible factors
Anaerobic glycolysis
030220 oncology & carcinogenesis
Sirtuin
biology.protein
Cancer research
CCAAT-Enhancer-Binding Proteins
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 452
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....4608b5c428b7aec84df0d448a245f06e