Conclusion
Our study provides evidence that silencing FOXM1 inhibits stemness of LCSCs by decreasing the expression of ALDH2, and represses the proliferation, migration, invasion, and tumorigenesis while inducing the apoptosis of LCSCs.
Methods
CD133+ CD24+ LCSCs were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. Proliferation-, epithelial-mesenchymal transition (EMT)-, apoptosis-, and stemness-related factors were then detected by western blot analysis. Tumor xenograft in nude mice was used to figure out the role of FOXM1 in tumorigenesis in vivo by regulating ALDH2 expression. Luciferase activity assay was conducted to determine whether FOXM1 could target ALDH2 promoter region and thereby affecting ALDH2 expression.
Objective
This study is performed to explore the role of transcription factor FOXM1 in promoting the self-renewal and proliferation of liver cancer stem cells (LCSCs) by regulating the expression of acetaldehyde dehydrogenase-2 (ALDH2).
Results
The sorted CD133+ CD24+ Huh-7 cells had the characteristic of stem cells. FOXM1 was highly expressed in CD133+ CD24+ Huh-7 cells. Silencing FOXM1 inhibited the proliferation and colony formation of LCSCs and decreased the expression of proliferating cell nuclear antigen and Ki-67 protein; inhibited the migration, invasion, and EMT of LCSCs while promoting the apoptosis of LCSCs, as well as promoted the expression of Bax and cleaved-caspase-3, and inhibited the expression of Bcl-2. Silencing FOXM1 inhibited the expression of Nanog, Oct4, and Sox2 in LCSCs by decreasing the expression of ALDH2. in vivo experiment, silencing FOXM1 suppressed tumorigenesis of LCSCs by decreasing the expression of ALDH2.