MiR-4269 suppresses the tumorigenesis and development of pancreatic cancer by targeting ZEB1/OTX1 pathway

Biosci Rep. 2020 Jun 26;40(6):BSR20200010. doi: 10.1042/BSR20200010.

Abstract

As one of the most prevalent malignant tumors, pancreatic cancer (PC) is a leading fatal cancer worldwide. Surging evidence has unraveled that miRNAs are involved in the occurrence and progression of multiple cancers, including PC. The tumor suppressor effects of miR-4269 have been certified in gastric carcinoma. However, the potential function of miR-4269 remains largely unclear, which drives us to identify the role of miR-4269 in PC development. In the present study, we determined the expression pattern of miR-4269 in PC cells and normal cells. Results of RT-qPCR analysis illuminated that miR-4269 expression level in PC cells was lower than that in normal cells. Functional assays demonstrated that up-regulation of miR-4269 obviously inhibited the proliferation, migration and invasion of PC cells. In order to elucidate the mechanism governing miR-4269 in PC, we carried out bioinformatics analysis and further experimental investigations. Our results validated that ZEB1 was a direct target of miR-4269. Additionally, ZEB1 activated the transcription of OXT1. More importantly, miR-4269 attenuated the expression level of OXT1 via targeting ZEB1. Ultimately, our findings confirmed that miR-4269 served as a cancer suppressor in PC through regulation of ZEB1/OTX1 pathway, which suggested that miR-4269 might represent a promising target for the clinical treatment of PC.

Keywords: OTX1; ZEB1; miR-4269; pancreatic cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Otx Transcription Factors / genetics
  • Otx Transcription Factors / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Signal Transduction
  • Transcription, Genetic
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • MIRN4269 microRNA, human
  • MicroRNAs
  • OTX1 protein, human
  • Otx Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1