miRNA‑205‑5p functions as a tumor suppressor by negatively regulating VEGFA and PI3K/Akt/mTOR signaling in renal carcinoma cells

Oncol Rep. 2019 Nov;42(5):1677-1688. doi: 10.3892/or.2019.7307. Epub 2019 Sep 10.

Abstract

MicroRNAs (miRNAs) are involved in the development of various types of cancers. Dysregulation of miR‑205‑5p has been reported in various types of human cancer. However, little is known concerning the role of miR‑205‑5p in renal cell carcinoma (RCC). The pr~esent study was designed to investigate the role of miR‑205‑5p in RCC. The expression of miR‑205‑5p was measured in clear cell renal cell carcinoma (ccRCC) tissues and cell lines using RT‑qPCR. RCC cell lines were transfected with miR‑205‑5p mimics. CCK‑8 assays, wound healing assays, Matrigel invasion assays and nucleosome ELISAs were used to assess the effects of miR‑205‑5p on cell growth, migration, invasion and apoptosis, respectively. Western blotting was employed to detect changes in protein levels. Bioinformatic analyses and luciferase reporter assays were performed to identify the potential targets of miR‑205‑5p. Mouse xenograft models were used to verify the effect of miR‑205‑5p in vivo. The expression of miR‑205‑5p was found to be downregulated in 25 RCC tissues compared to that noted in the adjacent normal tissues. Decreased expression of miR‑205‑5p was associated with poor clinical outcomes. Based on the results of the in vitro experiments, overexpression of miR‑205‑5p reduced RCC cell proliferation, invasion and migration. Overexpression of miR‑205‑5p also promoted apoptosis and inhibited the EMT in RCC cells. Moreover, the PI3K/Akt signaling pathway was found to be negatively regulated by miR‑205‑5p. Bioinformatic analyses and luciferase reporter assays revealed that miR‑205‑5p directly targeted the 3'‑UTR of vascular endothelial growth factor A (VEGFA). Furthermore, miR‑205‑5p negatively regulated the expression of VEGFA in ccRCC cell lines. In ccRCC tissues, miR‑205‑5p expression was inversely correlated with VEGFA expression. Moreover, overexpression of miR‑205‑5p inhibited RCC growth in vivo in a mouse xenograft model. Overall, miR‑205‑5p functions as a tumor suppressor in RCC by targeting VEGFA and the PI3K/Akt signaling pathway, providing a potential therapeutic target for the treatment of ccRCC.

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Survival Analysis
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • MIRN205 microRNA, human
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases