YB-1 expression promotes pancreatic cancer metastasis that is inhibited by microRNA-216a

Exp Cell Res. 2017 Oct 15;359(2):319-326. doi: 10.1016/j.yexcr.2017.07.039. Epub 2017 Aug 3.

Abstract

Pancreatic cancer is one of the most aggressive cancers. The vast majority of patients are diagnosed with advanced, unresectable disease because of early invasive growth and metastatic spread. The aim of this study was to examine YB-1 expression in pancreatic cancer and determine its effects on cell invasion. YB-1 is overexpressed in pancreatic cancer cell lines and patient tissue samples. In patient tissues, high YB-1 levels correlated with perineural invasion. Silencing of YB-1 significantly reduced cell invasion with decreased expression of MMPs in vitro. Furthermore, we found that the expression of YB-1 was suppressed by miR-216a via direct binding to the YB-1 3'-untranslated region. MiR-216a and YB-1 expression levels were inversely correlated in pancreatic cancer cell lines. In addition, ectopic expression of miR-216a inhibited cell invasion in vitro. Taken together, our findings suggest that YB-1 may play an important role in mediating metastatic behaviour and that repression of YB-1 by miR-216a could have a promising therapeutic potential to inhibit tumor metastasis in pancreatic cancer.

Keywords: Invasion; MiR-216a; Pancreatic cancer; Y-box-binding protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Apoptosis
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Y-Box-Binding Protein 1 / antagonists & inhibitors
  • Y-Box-Binding Protein 1 / genetics*
  • Y-Box-Binding Protein 1 / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN216 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Y-Box-Binding Protein 1
  • YBX1 protein, human