Effect of miR-590-3p/DKK1 Axis on the Progression of Wilms' Tumour

Arch Esp Urol. 2024 Mar;77(2):135-141. doi: 10.56434/j.arch.esp.urol.20247702.18.

Abstract

Background: Wilms' tumour is the most prevalent abdominal malignancy in children. This study focused on the mechanism of the miR-590-3p/Dickkopf 1 (DKK1) axis in Wilms' tumour.

Methods: The mRNA levels of miR-590-3p and DKK1 in 49 pairs of Wilms' tumour pathological specimens and normal tissues were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Wilms' tumour cells' invasion ability and proliferative ability were assessed using a Transwell assay and Cell Counting Kit-8 (CCK-8) assay, respectively. Dual-luciferase assay was performed to evaluate the potential relationship between miR-590-3p and DKK1 in Wilms tumour. Furthermore, a mouse transplanted tumour model was constructed to explore the function of miR-590-3p inhibitor on Wilms' tumour growth in vivo.

Results: DKK1 emerged as a target gene of miR-590-3p in Wilms' tumour. DKK1 expression was downregulated (p < 0.01), but miR-590-3p was overexpressed (p < 0.01) in Wilms' tumour tissues compared to normal tissues. miR-590-3p overexpression accelerated Wilms' tumour invasive ability and cell proliferation (p < 0.01). Additionally, DKK1 partially reversed miR-590-3p-induced proliferation (p < 0.05) and invasion ability (p < 0.01). Furthermore, downregulation of miR-590-3p restrained the growth rate of transplanted tumours in nude mice (p < 0.01).

Conclusions: Through the regulation of DKK1, miR-590-3p accelerated the invasion and proliferation of Wilms' tumour. The study suggests that the miR-590-3p/DKK1 axis represents a novel mechanism in Wilms' tumour.

Keywords: DKK1; Wilms’ tumour; miR-590-3p.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Child
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Wilms Tumor* / genetics
  • Wilms Tumor* / metabolism
  • Wilms Tumor* / pathology

Substances

  • MicroRNAs
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN590 microRNA, human