Zinc finger protein 91 accelerates tumour progression by activating β-catenin signalling in pancreatic cancer

Cell Prolif. 2021 May;54(5):e13031. doi: 10.1111/cpr.13031. Epub 2021 Mar 23.

Abstract

Objectives: ZFP91, an E3 ligase, has been reported to possess cancer-promoting functions. This study aimed to elucidate the exact role of ZFP91 in tumour progression of pancreatic cancer and underlying mechanisms.

Materials and methods: We analysed the correlation between ZFP91 expression and pancreatic cancer through TCGA and GEO data sets. Growth curve, colony formation, wound healing and transwell invasion assays were conducted to evaluate proliferation, migration and invasion of lentivirus transfected pancreatic cancer cells. GSEA and Western blot analysis were performed to validate the regulatory effect of ZFP91 on β-catenin. Drug response curve and orthotopic implantation model reflected the sensitivity of chemotherapies.

Results: ZFP91 overexpression is prevalent in pancreatic cancer and negatively correlated with overall survival. ZFP91 knock-down attenuated proliferation, migration and invasion of pancreatic cancer cells. β-catenin was a downstream gene of ZFP91, and its agonist could reverse the phenotype. ZFP91 promoted EMT and chemoresistance in pancreatic cancer.

Conclusions: We demonstrated that ZFP91 promoted pancreatic cancer proliferation, migration and invasion through activating β-catenin signalling. EMT and chemoresistance were also regulated by ZFP91. ZFP91 might be a potential therapeutic target for pancreatic cancer.

Keywords: bioinformatics; chemoresistance; pancreatic cancer; tumour biology; zinc finger protein 91; β-catenin.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition
  • Fluorouracil / therapeutic use
  • Humans
  • Imidazoles / pharmacology
  • Irinotecan / therapeutic use
  • Isoxazoles / pharmacology
  • Kaplan-Meier Estimate
  • Leucovorin / therapeutic use
  • Mice
  • Mice, Nude
  • Oxaliplatin / therapeutic use
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • Transplantation, Heterologous
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • 5-furan-2yl-isoxazole-3-carboxylic acid (3-imidazol-1yl-propyl)-amide
  • Imidazoles
  • Isoxazoles
  • RNA, Small Interfering
  • beta Catenin
  • folfirinox
  • Oxaliplatin
  • Irinotecan
  • Ubiquitin-Protein Ligases
  • ZFP91 protein, human
  • Leucovorin
  • Fluorouracil