Krüpple-like factor 10 regulates radio-sensitivity of pancreatic cancer via UV radiation resistance-associated gene

Vincent Hung Shu Chang, Yi Chih Tsai, Ya Li Tsai, Shu Ling Peng, Su Liang Chen, Tsung Ming Chang, Winston Chun Yuan Yu, Hui Ju Ch'ang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background and purpose Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. Materials and methods Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay. Orthotopic murine tumor model and clinical specimens were used to evaluate radio-sensitivity of pancreatic cancer. Results We found Klf10 silencing correlates with enhanced pancreatic cancer clonogenic survival and murine tumor growth after radiation. UVRAG was an essential down-stream mediator transcriptionally suppressed by Klf10. Silencing UVRAG mRNA in Klf10 depleted Panc-1 cells reversed the radio-resistant phenotypes including decreased apoptosis and enhanced DNA repair as well as autophagy. Metformin, an anti-diabetic agent, was found to increase Klf10 and suppress UVRAG expression to improve radiation cytotoxicity in pancreatic cancer. The predictive value of Klf10 in radiation response and the inverse correlation with UVRAG were confirmed in cohorts of pancreatic cancer patients. Conclusions Klf10 is a potential biomarker in predicting and sensitizing radiation effect in pancreatic cancer.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalRadiotherapy and Oncology
Volume122
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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