miRNA-205 is a candidate tumor suppressor that targets ZEB2 in renal cell carcinoma

Oncol Res Treat. 2014;37(11):658-64. doi: 10.1159/000368792. Epub 2014 Oct 17.

Abstract

Background: This study aims to characterize the function of downregulated MicroRNA miR-205 in renal cell carcinoma (RCC), and show how the downstream zinc finger E-box-binding homeobox 2 (ZEB2) is negatively regulated by miR-205.

Materials and methods: The expression of miR-205 was detected in RCC and adjacent non-tumor tissues using real-time polymerase chain reaction (PCR). The expression of miR-205 and ZEB2 was detected in RCC cell lines using real-time PCR. The luciferase reporter assay was used to assess ZEB2 as a target of miR-205. Protein levels of ZEB2, E-cadherin, and vimentin were measured by western blot after overexpression of miR-205 in ACHN cells. In vivo functions of miR-205 in ACHN cells were measured by MTT assays, migration and invasion assays, and flow cytometry.

Results: MiR-205 was significantly downregulated in RCC samples and cell lines compared with matched non-tumor tissues and HK-2 cells, respectively. No significant difference was found in miR-205 expression between well differentiated and poorly to moderately differentiated groups or between phase I and phase II-III. ZEB2 was upregulated in RCC cell lines compared with expression in HK-2 cells. Upregulation of miR-205 expression caused the downregulation of ZEB2 and vimentin, and the upregulation of E-cadherin in ACHN cells. miR-205 also inhibited proliferation, migration, and invasion, and induced apoptosis of ACHN cells.

Conclusion: miR-205 is a candidate tumor suppressor that targets ZEB2 in RCC.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Blotting, Western
  • Cadherins / metabolism
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation / physiology
  • Female
  • Flow Cytometry
  • Genes, Tumor Suppressor / physiology*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Vimentin / metabolism
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • Cadherins
  • Homeodomain Proteins
  • MIRN205 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Vimentin
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2