Forkhead box K2 (FOXK2) was first identified as an NFAT-like interleukin-binding factor. FOXK2 has been reported to act as either oncogene or tumor suppressor. However, functional and regulating mechanisms of FOXK2 in epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. An FOXK2-specific siRNA was employed to decrease the endogenous expression of FOXK2. MTT assay, colony formation and transwell assay were used to evaluate proliferation, migration and invasion of Hep3B and HCCLM3 cells, respectively. The protein expression associated with EMT and Akt signaling pathways was evaluated using western blot. FOXK2 downregulation could inhibit cell proliferation and colony formation and suppress migration and invasion in Hep3B and HCCLM3 cells. The expression of E-cadherin was significantly upregulated, and the expression of snail and p-Akt was significantly downregulated in siFOXK2-transfected cells compared with control cells. SF1670 induced the expression of p-Akt and snail and suppressed the expression of E-cadherin in Hep3B and HCCLM3 cells. SF1670 promoted the invasion and colony formation of Hep3B and HCCLM3 cells. SF1670 partly inhibited the effect of FOXK2 suppression on Hep3B and HCCLM3 cells. In conclusion, this study revealed that FOXK2 downregulation suppressed the EMT in HCC partly through inhibition of the Akt signaling pathway.
Keywords: Akt; FOXK2; epithelial–mesenchymal transition; hepatocellular carcinoma.
© 2020 Jian Kong et al., published by De Gruyter.