A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4

Pancreas. 2015 Apr;44(3):370-9. doi: 10.1097/MPA.0000000000000283.

Abstract

Objectives: Pancreatic cancer is an aggressive cancer with high mortality. Conventional treatments have little impact on its progression. Limited research investigating the role of oncogene miR-150 specifically in pancreatic cancer has been published. The purpose of this study was to determine the tumorigenesis of miR-150 in pancreatic cancer.

Methods: One hundred six pancreatic ductal adenocarcinomas were analyzed together with their adjacent benign pancreatic tissues. The associations of miR-150, c-Myb, and MUC4 expression with survival rates were determined. Functional studies on miR-150 in pancreatic cancer were used to assess its effect on proliferation and malignancy in several pancreatic cell lines.

Results: miR-150 expression was significantly down-regulated in pancreatic ductal adenocarcinoma tissues compared with adjacent benign pancreatic tissues. Patients with low miR-150 expression had significantly higher mortality rates than those with high miR-150 expression. The in vitro and in vivo assays of pancreatic cancer cells showed that miR-150 overexpression leads to reduced cell growth, clonogenicity, migration, invasion, modular cell cycles, and induced apoptosis. Moreover, miR-150 expression was inversely correlated with c-Myb and MUC4 activities in pancreatic tissue, cell lines, and nude mouse model.

Conclusions: miR-150 is an important suppressor of pancreatic ductal carcinoma and acts as a regulator of c-Myb and MUC4 in aggressive progress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mucin-4 / genetics
  • Mucin-4 / metabolism*
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism*
  • RNA Interference
  • Signal Transduction
  • Survival Rate
  • Time Factors
  • Transfection

Substances

  • MIRN150 microRNA, human
  • MUC4 protein, human
  • MicroRNAs
  • Mucin-4
  • Proto-Oncogene Proteins c-myb