MiR-940 inhibited pancreatic ductal adenocarcinoma growth by targeting MyD88

Cell Physiol Biochem. 2015;35(3):1167-77. doi: 10.1159/000373941. Epub 2015 Feb 6.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is an almost universally lethal disease. Deregulation or dysfunction of miRNAs contribute to cancer development. The role of miR-940 in PDAC remains unclear.

Methods: The level of miR-940 in PDAC tissues and cell lines was measured by qRT-PCR. MiR-940 was over-expressed by miRNAs mimics transfection and reduced by miRNAs antisense oligonucleotides (ASO) transfection. Cell proliferation was analyzed by MTT assay and cell apoptosis was evaluated by FACS analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Myeloid differentiation primary response gene (88) (MyD88) protein level was assayed by immunohistochemistry and Western blot analysis.

Results: Low miR-940 level and high MyD88 protein level in PDAC tissues were both correlated with low survival rate. Up-regulation of miR-940 inhibited PDAC cell lines growth while down-regulation induced cell growth. The 3' UTR of MyD88 was targeted by miR-940.

Conclusions: Low level of miR-940 and high level of MyD88 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-940 exerted its effect by targeting MyD88.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Apoptosis / genetics
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Myeloid Differentiation Factor 88 / biosynthesis*
  • Myeloid Differentiation Factor 88 / genetics
  • Oligonucleotides, Antisense / administration & dosage

Substances

  • MIRN940 microRNA, human
  • MYD88 protein, human
  • MicroRNAs
  • Myeloid Differentiation Factor 88
  • Oligonucleotides, Antisense