DEP domain containing 1 suppresses apoptosis via inhibition of A20 expression, which activates the nuclear factor κB signaling pathway in HepG2 cells.

Abstract

A previous study revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis of bladder cancer via forming a complex with zinc finger protein 224 (ZNF224) to suppress A20 expression, resulting in the activation of the nuclear factor (NF)-κB signaling pathway; however, the role of DEPDC1 in liver cancer remains unclear. Hep G2 cells were treated with 11R-DEP: 611–628, a peptide capable of disrupting the DEPDC1-ZNF224 complex. Cell proliferation was examined using an MTT assay and apoptosis was analyzed via detection of the apoptotic marker caspase-3 using western blot analysis. A20 expression was examined via reverse transcription-quantitative polymerase chain reaction and NF-κB subcellular localization was determined via immunofluorescence staining. microRNA (miR)-130a was overexpressed in HepG2 cells and its effects on proliferation and apoptosis were examined. The results demonstrated that 11R-DEP: 611–628 (3 µM) and miR-130a inhibited cell proliferation and promoted apoptosis in HepG2 cells by activating A20 expression, which blocks the nuclear transportation of NF-κB. In addition, the results demonstrated that the 11R-DEP: 611–628 (3 µM) treatment resulted in downregulation of DEPDC1 expression, indicating that DEPDC1 expression is regulated by the DEPDC1-ZNF224 complex. In conclusion, the data indicated that DEPDC1 suppresses apoptosis to promote cell proliferation through the NF-κB signaling pathway in HepG2 cells and that DEPDC1 is a potential target for the treatment of liver cancer.