Knockout of CTNNB1 by CRISPR-Cas9 technology inhibits cell proliferation through the Wnt/β-catenin signaling pathway

Biotechnol Lett. 2018 Mar;40(3):501-508. doi: 10.1007/s10529-017-2491-2. Epub 2017 Dec 16.

Abstract

Objective: To study the effects of CTNNB1 gene knockout by CRISPR-Cas9 technology on cell adhesion, proliferation, apoptosis, and Wnt/β-catenin signaling pathway.

Results: CTNNB1 gene of HEK 293T cells was knocked out by CRISPR-Cas9. This was confirmed by sequencing and western blotting. Methylthiazolyl-tetrazolium bromide assays indicated that deletion of β-catenin significantly weakened adhesion ability and inhibited proliferation rate (P < 0.01) of HEK 293T cells. Nevertheless, deletion of β-catenin did not affect apoptosis of HEK 293T cells, which was analyzed by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. In addition, expression level of GSK-3β, CCND1, and CCNE1 detected by qPCR and expression level of N-Cadherin and cyclin D1 detected by western blotting were significantly decreased (P < 0.01) while expression of γ-catenin detected by western blotting was significantly increased (P < 0.001).

Conclusions: Knockout of CTNNB1 disturbed Wnt/β-catenin signaling pathway and significantly inhibited adhesion and proliferation of HEK 293T cells.

Keywords: CRISPR-Cas9; CTNNB1; Cell adhesion; Cell proliferation; Wnt/β-catenin signaling pathway; β-catenin.

MeSH terms

  • Apoptosis
  • CRISPR-Cas Systems / genetics*
  • Cell Adhesion
  • Cell Proliferation / genetics*
  • Gene Editing
  • HEK293 Cells
  • Humans
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • beta Catenin