MiR-539 functions as a tumor suppressor in pancreatic cancer by targeting TWIST1

Exp Mol Pathol. 2019 Jun:108:143-149. doi: 10.1016/j.yexmp.2019.04.012. Epub 2019 Apr 22.

Abstract

The dysregulation of microRNA (miRNA) expression has been highlighted in a variety of human malignant conditions with reports implicating a critical role in the process of tumor growth. The role of miR-539 in pancreatic cancer (PC) is yet to be fully elucidated, hence the aim of the current study was to investigate the effect of miR-539 expression in relation to a cohort of 52 PC specimens. The application of a real-time quantitative polymerase chain reaction (qRT-PCR) revealed a significantly down-regulated miR-539 level, which was accompanied by an increased TWIST1 expression in PC when compared with the controls. The in vitro experiment results demonstrated that the endogenic mimic of miR-539 significantly suppressed the growth of the xenograft tumors in PANC-1 cells, when compared to the delivery of the control miRNA and blank control. Meanwhile, the key epithelial-mesenchymal transition (EMT) inducer, TWIST1 was verified as a direct target gene of miR-539 through the application of a luciferase reporter assay. In conclusion, the results of the current study present evidence emphasizing the significance of the interactions between miR-539 and TWIST1 in the development of and progression of PC, highlighting its potential as a therapeutic target in the treatment of PC patients.

Keywords: Epithelial-mesenchymal transition; Pancreatic cancer; TWIST1; miR-539.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Transcriptome
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN539 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1