Overexpression of KLF5 is associated with poor survival and G1/S progression in pancreatic cancer

Aging (Albany NY). 2019 Jul 21;11(14):5035-5057. doi: 10.18632/aging.102096.

Abstract

Despite improvements in surgical procedures and comprehensive therapies, pancreatic cancer remains one of the most aggressive and deadly human malignancies. It is therefore necessary to determine which cellular mediators associate with prognosis in pancreatic cancer so as to improve the treatment of this disease. In the present study, mRNA array and immunohistochemical analyses showed that KLF5 is highly expressed in tissue samples from three short-surviving patients with pancreatic cancer. Survival analysis using data from The Cancer Genome Atlas showed that patients highly expressing KLF5 exhibited shorter overall and tumor-free survival times. Mechanistically, KLF5 promoted expression of E2F1, cyclin D1 and Rad51, while inhibiting expression of p16 in pancreatic cancer cells. Finally, flow cytometric analyses verified that KLF5 promotes G1/S progression of the cell cycle in pancreatic cancer cells. Collectively, these findings demonstrate that KLF5 is an important prognostic biomarker in pancreatic cancer patients, and they shed light on the molecular mechanism by which KLF5 stimulates cell cycle progression in pancreatic cancer.

Keywords: KLF5; long-term survival; microRNA; pancreatic cancer; short-term survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • E2F1 Transcription Factor / genetics
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kruppel-Like Transcription Factors*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Prognosis
  • Rad51 Recombinase / genetics
  • Survival Analysis
  • Transcriptome

Substances

  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • KLF5 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • Cyclin D1
  • RAD51 protein, human
  • Rad51 Recombinase