MicroRNA-183 promotes proliferation and invasion in oesophageal squamous cell carcinoma by targeting programmed cell death 4

Br J Cancer. 2014 Nov 11;111(10):2003-13. doi: 10.1038/bjc.2014.485. Epub 2014 Sep 11.

Abstract

Background: Dysregulated microRNAs (miRNAs) can serve as oncogenes or suppressors and are associated with many cancers, including oesophageal squamous cell carcinoma (ESCC).

Methods: An alignment miRNA array was used to identify differentially expressed miRNAs in ESCC tissues. The expression of miR-183 and programmed cell death 4 (PDCD4) in oesophageal tissues from ESCC and early oesophageal carcinoma patients was examined by quantitative reverse transcriptase PCR and western blotting. A luciferase assay was performed to confirm miR-183 target genes. The effects of miR-183 on ESCC cells and the associated mechanisms were established by in vitro experiments.

Results: We identified 51 upregulated miRNAs and 17 downregulated miRNAs in our array, and miR-183 was one of the most upregulated miRNAs. An inverse correlation between miR-183 and PDCD4 levels was found in ESCC tissues. Upregulated expression of miR-183 was not correlated with tumour stage or lymphatic metastasis in ESCC patients. The luciferase assay confirmed that miR-183 directly interacted with the PDCD4 mRNA 3'-untranslated region in ESCC cells. Overexpression of miR-183 led to decreased PDCD4 protein levels and promoted ESCC cell proliferation and invasion. Inhibition of the PI3K/Akt signalling pathway increased PDCD4 protein levels and decreased miR-183 expression in ESCC cells.

Conclusions: MiR-183 promotes ESCC cell proliferation and invasion by directly targeting PDCD4, which suggests that it is involved in the pathogenesis of ESCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophagus / metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Tumor Cells, Cultured

Substances

  • Apoptosis Regulatory Proteins
  • MIRN183 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins