miR-23a acts as an oncogene in pancreatic carcinoma by targeting FOXP2

J Investig Med. 2018 Mar;66(3):676-683. doi: 10.1136/jim-2017-000598. Epub 2017 Nov 14.

Abstract

MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. FOXP2 expression was downregulated and inversely correlated with miR-23a. miR-23a directly targeted the 3'-untranslated region of FOXP2 mRNA and repressed its expression. Mechanistically, enhancement of miR-23a by transfection with mimics in Aspc-1 cells significantly promoted cell proliferation and invasion, while miR-23a inhibitors transfection in SW1990 cells induced an inhibitory effect. Moreover, restoration of FOXP2 impaired the pro-proliferation and proinvasion effects of miR-23a, indicating FOXP2 is a direct mediator of miR-23a functions. In conclusion, our findings suggest a novel miR-23a/FOXP2 link contributing to PDAC development and invasion. It may be a potential diagnostic and therapeutic target for PDAC.

Keywords: FOXP2; invasion; miR-23a; proliferation.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Oncogenes*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology

Substances

  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • MIRN23a microRNA, human
  • MicroRNAs