Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China
Correspondence:
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Corresponding author: Chunqing Dou, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China. E-mail: cqdou@sina.com.
Abstract: OBJECTIVE: The transcription factor FOXF2 is reported to be down-regulated in HCC. Its deficiency is correlated with shorter disease-free survival and overall survival of HCC patients; however, the mechanism remains to be elucidated. MATERIALS AND METHODS: In this study, we performed qRT-PCR and western blotting to confirm the down-regulated FOXF2 in HCC tissue and cell lines. Then the HCC cell line Huh7 transduced with FOXF2 shRNA was adopted in a series of in vitro and in vivo assays to evaluate the cell phenotype change, migration, invasion, proliferation, colonization of circulating cell and the formation of metastatic nodules. RESULTS: We found that FOXF2 was down-regulated in HCC tissues and cell lines. FOXF2 deficiency in Huh7 cells increased E-cadherin and decreased Vimentin. The down-regulation of FOXF2 impeded HCC cell migration and invasion capacity, but promoted the proliferation of HCC cells and the growth of subcutaneous tumors in nude mice, which indicated a mesenchymal-to-epithelial phenotypic change in Huh7 cells. FOXF2 deficiency enhanced the colonization of circulating HCC cell, thus promoted the formation of metastatic nodules. CONCLUSIONS: FOXF2 deficiency induced mesenchymal-epithelial transition (MET) in Huh7 cell which might facilitate the colonization of circulating tumor cells and the formation of metastasis.
