MiRNA-545 negatively regulates the oncogenic activity of EMS1 in gastric cancer

Cancer Med. 2018 Jun;7(6):2452-2462. doi: 10.1002/cam4.1520. Epub 2018 May 7.

Abstract

Gastric cancer (GC) is a common malignant tumor of the digestive system. In addition, GC metastasis is an extremely complicated process. In this article, high expression levels of EMS1 mRNA and protein were found to be positively correlated with an enhanced malignant potential of GC cells and a poor clinical prognosis of GC patients. Interestingly, the expression levels of EMS1 mRNA and protein in GC cells were inhibited by microRNA-545 (miR-545), which was identified by a bioinformatics analysis. The expression level of miR-545 in carcinoma tissues was significantly lower than that in para-carcinoma tissues. The proliferation and epithelial-mesenchymal transition (EMT) of GC cells were suppressed by exogenous oligonucleotides of miR-545 mimics. In addition, the expression levels of EMT-associated markers were altered with the expression of miR-545. Notably, the growth rates of tumors in nude mice were seriously restrained by an intratumoral injection of oligonucleotides of the miR-545 mimics. These results suggest a negative regulatory role of miR-545 on the oncogenic activity of EMS1. In addition, EMS1 and miR-545 may be potential biomarkers for GC diagnosis. Synthesized oligonucleotides of miR-545 mimics may be developed as important gene medicines for GC therapy in the future.

Keywords: Cell proliferation; EMS1; EMT process; gastric cancer; miR-545.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cortactin / genetics*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA Interference*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • CTTN protein, human
  • Cortactin
  • MIR545 microRNA, human
  • MicroRNAs