Effects of targeted silencing of FOXC1 gene on proliferation and in vitro migration of human non-small-cell lung carcinoma cells.

Background: The aim of this study was to evaluate the effects of targeted silencing of forkhead box C1 (FOXC1) gene with small interfering RNA (siRNA) on the proliferation and in vitro migration of human non-small-cell lung carcinoma (NSCLC) A549 and NCIH460 cells, and to explore the molecular mechanism.

Methods: These cells were divided into FOXC1 siRNA groups and negative control groups.

Results: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) showed that compared with normal cells and paracancerous tissues, FOXC1 mRNA expressions in NSCLC cells and tissues were significantly higher (P<0.05). qRT-PCR and Western blot showed that FOXC1 siRNA effectively silenced FOXC1 gene expression in NSCLC cells. EdU labeling assay revealed that the proliferative capacity significantly decreased compared with that of normal control group after FOXC1 silencing (P<0.05). Significantly fewer cells in the transfected group migrated than those in negative control group did. After FOXC1 silencing, NSCLC cells were arrested in the G0/G1 phase, which were significantly different from those in negative control group (P<0.05). Compared with negative control group, the expression of cyclin D1 decreased and that of E-cadherin increased. Meanwhile, vimentin and MMP-2 expressions significantly reduced (P<0.05). FOXC1 siRNA effectively silenced FOXC1 gene expressions in NSCLC cells, inhibited their proliferation and invasion, and arrested them in the G0/G1 phase, suggesting that FOXC1 affected proliferation probably by regulating the expression of cell cycle-related protein cyclin D1.

Conclusion: Silencing FOXC1 may evidently inhibit the migration of these cells by reversing the EMT process through suppressing cadherin, being associated with the expressions of extracellular MMPs.