Up-regulation of UHRF1 by oncogenic Ras promoted the growth, migration, and metastasis of pancreatic cancer cells

Mol Cell Biochem. 2015 Feb;400(1-2):223-32. doi: 10.1007/s11010-014-2279-9. Epub 2014 Nov 23.

Abstract

Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) has been reported as a marker for the differential diagnosis of pancreatic cancer and chronic pancreatitis. However, the expression pattern and biological functions of UHRF1 in the progression of pancreatic cancer are not fully understood. In this study, it was found that the expression of UHRF1 was significantly up-regulated in pancreatic cancer samples compared to their adjacent normal tissues. Meanwhile, the expression of UHRF1 was inversely correlated with the survival of pancreatic cancer patients. Moreover, in the biological function studies, UHRF1 was shown to promote the growth, migration, and metastasis of pancreatic cancer cells in vitro and in vivo. Mechanistically, the expression of UHRF1 was induced by oncogenic Ras in both pancreatic cancer mouse model and cultured cells. Taken together, our study demonstrated that UHRF1 played an oncogenic role in the progression of pancreatic cancer, and UHRF1 might be a promising target for the treatment of pancreatic cancer.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / biosynthesis*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, ras / genetics*
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Ubiquitin-Protein Ligases
  • Xenograft Model Antitumor Assays

Substances

  • CCAAT-Enhancer-Binding Proteins
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases