MiR-205 mediated APC regulation contributes to pancreatic cancer cell proliferation

World J Gastroenterol. 2019 Jul 28;25(28):3775-3786. doi: 10.3748/wjg.v25.i28.3775.

Abstract

Background: Pancreatic cancer is a deadly malignancy with aggressive properties. MicroRNAs (miRNAs) participate in the pathogenesis of a variety of diseases and molecular processes by targeting functional mRNAs. Nevertheless, the regulatory role of miRNAs in signaling pathways involved in pancreatic cancer remains largely unknown.

Aim: To explore the molecular regulation involved in pancreatic cancer and potential mechanisms of miR-205.

Methods: Microarray analysis was performed to investigate the expression profile of miRNAs in pancreatic cancer. Expression of miR-205 was validated by qRT-PCR. Target prediction and functional enrichment analysis were employed to seek potential target genes of miR-205 and potential functions of these genes. The target binding of miR-205 and adenomatous polyposis coli (APC) was validated by luciferase reporter assay. APC protein expression in pancreatic cancer was validated by qRT-PCR and Western blot. Proliferation was evaluated by MTT and colony formation assays.

Results: A large number of miRNAs with altered expression were identified in pancreatic cancer. MiR-205 was significantly up-regulated. APC was found to be a validated target of miR-205 and down-regulated in pancreatic cancer. Proliferation experiments showed that miR-205 could promote cell proliferation in pancreatic cancer by targeting APC.

Conclusion: The above findings suggested that miR-205 mediated APC regulation contributes to pancreatic cancer development, which could be considered as a novel prognostic biomarker for clinical care.

Keywords: Adenomatous polyposis coli; MiR-205; Microarray; Pancreatic cancer; Proliferation.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Primary Cell Culture
  • Prognosis
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Biomarkers, Tumor
  • MIRN205 microRNA, human
  • MicroRNAs