miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells

Br J Cancer. 2016 Sep 6;115(6):731-40. doi: 10.1038/bjc.2016.244. Epub 2016 Aug 18.

Abstract

Background: Dysregulation of microRNAs (miRNAs) has been found in human epithelial ovarian cancer (EOC). However, the role and mechanism of action of miR-23a in EOC remain unclear.

Methods: The roles of miR-23a, IKKα, and ST7L in EOC were determined by MTT, colony formation, wounding healing, transwell, flow cytometry, immunofluorescence, RT-qPCR, and western blotting experiments. miR-23a target genes were validated by EGFP reporter assays, RT-qPCR, and western blotting analysis.

Results: miR-23a is upregulated and promotes tumorigenic activity by facilitating the progress of cell cycle and EMT and repressing apoptosis in EOC cells. miR-23a enhances the expression of IKKα but suppresses the expression of ST7L by binding the 3'UTR of each transcript in EOC cells. The proliferation, migration, and invasion of EOC cells are increased by IKKα and inhibited by ST7L. Furthermore, miR-23a activates NF-κB by upregulating IKKα and WNT/MAPK pathway by downregulating ST7L.

Conclusions: miR-23a functions as an oncogene by targeting IKKα and ST7L, thus contributing to the malignancy of EOC cells.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • I-kappa B Kinase / biosynthesis
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / physiology*
  • MAP Kinase Signaling System / genetics
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA, Neoplasm / genetics*
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Tumor Suppressor Proteins
  • Wnt Signaling Pathway / genetics

Substances

  • 3' Untranslated Regions
  • MIRN23a microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • ST7L protein, human
  • Tumor Suppressor Proteins
  • I-kappa B Kinase