MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer

PLoS One. 2014 Aug 19;9(8):e104510. doi: 10.1371/journal.pone.0104510. eCollection 2014.

Abstract

Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3'UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transfection

Substances

  • 3' Untranslated Regions
  • MIRN410 microRNA, human
  • MicroRNAs
  • Luciferases
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2

Grants and funding

Anhui Provincial Natural Science Foundation (NO. 1208085QH169) http://220.178.98.52/zrkxjj/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.