MicroRNA-148a suppresses epithelial-mesenchymal transition and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway

Oncol Rep. 2017 Jul;38(1):301-308. doi: 10.3892/or.2017.5705. Epub 2017 Jun 6.

Abstract

Epithelial-mesenchymal transition (EMT) plays a critical role in the process of cancer invasion and metastasis. The Wnt/β-catenin signaling pathway is known as a stimulative factor, which may trigger EMT and metastasis of cancer cells. In addition, several microRNAs (miRNAs) have been proven to regulate the EMT process. Recent research revealed that miR‑148a is downregulated in pancreatic cancer. However, the definite role of miR-148a in EMT and invasion of pancreatic cancer is still unknown. The present study attempted to demonstrate the underlying mechanism of miR-148a in the regulation of EMT and invasion of pancreatic cancer cells. Our data revealed that the expression of miR-148a was markedly downregulated in human pancreatic ductal adenocarcinoma (PDAC) cell lines and tissues. In addition, the downregulation of miR-148a was associated with poor prognosis and EMT phenotype. Furthermore, restoration of miR-148a expression inhibited the EMT process, as well as the migration and invasion of BxPC-3 pancreatic cancer cells. Wnt10b, a promoting molecule of the Wnt/β-catenin signaling pathway, was demonstrated by dual‑luciferase reporter assay to be a direct target of miR‑148a. Subsequently, we found that miR‑148a negatively regulated the protein expression of β-catenin, cyclin D1 and MMP-9, which were important components of the Wnt/β-catenin signaling pathway. In conclusion, these findings revealed that miR-148a suppresses EMT and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway, and thus, miR-148a may serve as a novel therapeutic target for pancreatic cancer.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • Tumor Cells, Cultured
  • Wnt Proteins / antagonists & inhibitors*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • beta Catenin / antagonists & inhibitors*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MIRN148 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • WNT10B protein, human
  • Wnt Proteins
  • beta Catenin