MicroRNA‑199b promotes cell proliferation and invasion in Wilms' tumour by directly targeting Runt‑related transcription factor 3

Mol Med Rep. 2018 Aug;18(2):1812-1819. doi: 10.3892/mmr.2018.9096. Epub 2018 May 29.

Abstract

Emerging evidence has demonstrated that the deregulation of microRNAs (miRNAs) contributes to Wilms' tumour (WT) malignant progression. Therefore, identifying the essential miRNAs for WT onset and progression may be a promising therapeutic method for patients with this disease. Dysregulation of miRNA‑199b (miR‑199b) serves significant roles in various types of human cancer. However, its expression patterns, possible functions and associated mechanisms in WT are largely unknown. In the present study, the expression of miR‑199b in WT tissues was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. The biological functions of miR‑199b overexpression in WT cells were determined using Cell counting kit‑8 and Transwell invasion assays. The mechanisms underlying the action of miR‑199b in WT cells were also investigated using bioinformatics analysis, a luciferase reporter assay, RT‑qPCR and western blot analysis. It was revealed that miR‑199b expression was upregulated in WT tissues. In addition, the downregulation of miR‑199b attenuated the proliferation and invasion of WT cells. Runt‑related transcription factor 3 (RUNX3) was mechanistically predicted as a potential target of miR‑199b. Subsequent experiments demonstrated that RUNX3 was a direct target gene of miR‑199b in WT. In addition, the downregulation of RUNX3 in the WT tissues was inversely correlated with the miR‑199b expression level. The recovered RUNX3 expression counteracted the oncogenic roles of miR‑199b in WT cells. Therefore miR‑199b may serve as an oncogene in WT progression by directly targeting RUNX3, thereby suggesting that the miR‑199b/RUNX3 axis may be a promising therapeutic target for patients with WT.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Wilms Tumor / genetics*
  • Wilms Tumor / pathology

Substances

  • Core Binding Factor Alpha 3 Subunit
  • MicroRNAs
  • Runx3 protein, human
  • mirn199 microRNA, human