Oncogenic miR-23a in Pancreatic Ductal Adenocarcinogenesis Via Inhibiting APAF1

Dig Dis Sci. 2015 Jul;60(7):2000-8. doi: 10.1007/s10620-015-3588-x. Epub 2015 Feb 21.

Abstract

Background: miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not.

Aims: We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis.

Methods: miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively.

Results: Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3'UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects.

Conclusions: It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Apoptotic Protease-Activating Factor 1 / genetics
  • Apoptotic Protease-Activating Factor 1 / metabolism*
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Gene Expression Regulation / physiology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pancreatic Ducts / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • Biomarkers, Tumor
  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Messenger