Silencing FOXA1 gene regulates liver cancer cell apoptosis and cell proliferation.

OBJECTIVE: Liver cancer emerged as a major health problem, and it accounts for leading cancer-related death worldwide. Due to recurrence and metastatic behavior, it is challenging to be controlled and managed. Understanding the regulative role of different proteins, which regulates liver cancer in various pathological stages, is essential to be investigated. In this study, we analyzed the correlation between Foxa1 suppression along with apoptosis and cancer stem cell proliferation.

MATERIALS AND METHODS: CD133+ cells were used to induce the initial and advanced stage of liver cancer. Histology was used to study and confirm the tissue complications associated with initial, advanced and Foxa1 silenced liver cancer tissues. Immunohistochemistry and Western blotting were used to quantify Foxa1, CD133 expression. TUNEL assay was performed to study apoptosis.

RESULTS: Initially using CD133+ cells, we successfully developed a mouse model with the initial and advanced stage of liver cancer upon 4 and 8 weeks incubation. Histologically, as the tumor progress, it shows more proliferative cells with disorganized tissue structure. Foxa1 silencing aids in recovering from initial liver cancer, but it has only limited effects with advanced liver cancer. The apoptosis process is enhanced in initial liver cancer, and Foxa1 silenced tissue when compared with the advanced stage of liver cancer. Foxa1 silencing also suppresses the cancer stem cell proliferation.

CONCLUSIONS: Overall, our results reveal the critical role of Foxa1 in regulating apoptosis and liver cancer stem cells.