DRAM1 regulates the migration and invasion of hepatoblastoma cells via autophagy-EMT pathway.

Abstract

DNA-damage regulated autophagy modulator 1 (DRAM1) is known as a target of TP53-mediated autophagy, and has been reported to promote the migration and invasion abilities of glioblastoma stem cells. However, the precise contribution of DRAM1 to cancer cell invasion and migration, and the underlying mechanisms remain unclear. In the present study, small interfering (si)RNA or short hairpin RNA mediated knockdown of DRAM1 was performed in hepatoblastoma cells and the migration and invasion abilities were detected in vitro and in vivo. To investigate the underlying mechanisms, western blotting and immunofluorescence were used to detect the expression of autophagy-associated proteins and epithelial-mesenchymal-transition (EMT)-associated markers. The results showed that DRAM1 knockdown by specific siRNA abrogated cell autophagy, as well as inhibited the migration and invasion of HepG2 cells in Transwell assays, which may be reversed by rapamycin treatment. In addition, DRAM1 knockdown increased the expression of E-Cadherin while decreased the expression of vimentin in HepG2 cells, which was also be reversed by rapamycin treatment. Taken together, these results suggest that DRAM1 is involved in the regulation of the migration and invasion of HepG2 cells via autophagy-EMT pathway.