Kaiso (ZBTB33) Downregulation by Mirna-181a Inhibits Cell Proliferation, Invasion, and the Epithelial-Mesenchymal Transition in Glioma Cells

Cell Physiol Biochem. 2018;48(3):947-958. doi: 10.1159/000491963. Epub 2018 Jul 23.

Abstract

Background/aims: Kaiso (ZBTB33) expression is closely associated with the progression of many cancers and microRNA (miRNA) processing. MiR-181a plays critical roles in multiple cancers; however, its precise mechanisms in glioma have not been well clarified. The goal of this study was to evaluate the interaction between Kaiso and miR-181a in glioma.

Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the levels of Kaiso and miR-181a in glioma tissues and cell lines. Cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT) were evaluated to analyze the biological functions of miR-181a and Kaiso in glioma cells. The mRNA and protein levels of Kaiso were measured by qRT-PCR and western blotting, respectively. Meanwhile, luciferase assays were performed to validate Kaiso as a miR-181a target in glioma cells.

Results: We found that the level of miR-181a was the lowest among miR-181a-d in glioma tissues and cell lines, and the low level of miR-181a was closely associated with the increased expression of Kaiso in glioma tissues. Moreover, transfection of miR-181a significantly inhibited the proliferation, invasion, and EMT of glioma cells, whereas knockdown of miR-181a had the opposite effect. Bioinformatics analysis predicted that Kaiso was a potential target gene of miR-181a, and the luciferase reporter assay demonstrated that miR-181a could directly target Kaiso. In addition, Kaiso silencing had similar effects as miR-181a overexpression in glioma cells, whereas overexpression of Kaiso in glioma cells partially reversed the inhibitory effects of the miR-181a mimic. Conclusionss: miR-181a inhibited the proliferation, invasion, and EMT of glioma cells by directly targeting and downregulating Kaiso expression.

Keywords: EMT; Glioma; Invasion; Kaiso; MiRNA-181a; Proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Cadherins
  • MIRN-181 microRNA, human
  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • RNA, Small Interfering
  • Transcription Factors
  • ZBTB33 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9