Implication of BIS in the Migration and Invasion of A549 Non-small Cell Lung Cancer Cells

Abstract

Background/aim: High expression of the Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic protein, in various human cancers is linked to a poor outcome. The purpose of this study was to clarify whether BIS is associated with the migration and invasive characteristics of A549 cells.

Materials and methods: BIS-knockout (KO) cells were prepared by the CRISPR/Cas9 method. The aggressive behaviors of A549 cells were analyzed by wound healing and a transwell invasion assay as well as 3D spheroid culture.

Results: BIS depletion resulted in significant inhibition of the migration and invasive potential of A549 cells which was accompanied by an increased ratio of E-cadherin/N-cadherin and a decrease in the mRNA levels of Zeb1, Snail, Slug and MMP-2. NF-ĸB activity was suppressed in BIS-KO A549 cells due to the decrease in p65 protein levels, but not in mRNA levels.

Conclusion: BIS regulates cell invasion and the induction of the epithelial-mesenchymal transition (EMT) phenotype in A549 cells probably via the NF-ĸB signaling pathway.

Keywords: A549; BIS; EMT; NF-ĸB; invasion; migration.