MicroRNA-483-3p Promotes Proliferation, Migration, and Invasion and Induces Chemoresistance of Wilms' Tumor Cells

Pediatr Dev Pathol. 2020 Mar-Apr;23(2):144-151. doi: 10.1177/1093526619873491. Epub 2019 Sep 9.

Abstract

Wilms' tumor is the most common pediatric renal malignancy. MiRNAs are important regulators in multiple cancers including Wilms' tumor. In this study, we examined the role of miR-483-3p on proliferation, chemosensitivity, migration, and invasion of Wilms' tumor cells. The proliferation of Wilms' tumor cells was examined using WST-1 assay. The migration and invasion of Wilms' tumor cells were evaluated by transwell migration assay and matrigel invasion assay. The protein expression levels were detected by Western blot. The effect of miR-483-3p on doxorubicin-induced apoptosis in Wilms' tumor cells was evaluated by caspase-Glo3/7 assay. Forced expression of miR-483-3p promoted the proliferation, migration, and invasion in Wilms' tumor cells. Meanwhile, miR-483-3p decreased the sensitivity of Wilms' tumor cells after doxorubicin treatment. MiR-483-3p inhibited the doxorubicin-induced apoptosis in Wilms' tumor cells by the regulation of BAX and Bcl-2 expression. Furthermore, miR-483-3p regulated epithelial-mesenchymal transition by affecting the expression of E-cadherin, N-cadherin, snail, and vimentin in Wilms' tumor cells. Further studies showed that the expression levels of PTEN and p-AKT in Wilms' tumor cells were changed after aberrant expression of miR-483-3p by binding to 3'-UTR of PTEN. Our study suggests that miR-483-3p played important roles in proliferation and progression in Wilms' tumor cells and might serve as a potential prognostic biomarker and predict chemotherapy response in Wilms' tumor.

Keywords: AKT; Wilms’ tumor; apoptosis; miR-483-3p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / pathology*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Wilms Tumor / diagnosis
  • Wilms Tumor / drug therapy
  • Wilms Tumor / pathology*

Substances

  • 3' Untranslated Regions
  • MIRN483 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human