LASS2 inhibits proliferation and induces apoptosis in HepG2 cells by affecting mitochondrial dynamics, the cell cycle and the nuclear factor‑κB pathways

Abstract

LAG1 longevity assurance homolog 2 (LASS2) is a candidate biomarker in cancer that is dysregulated in various types of tumor, potentially affecting cell growth, invasion and migration. Although its effects on liver cancer metastasis and invasion have been reported, specific phenotypic studies and potential molecular mechanisms have not been completely elucidated in hepatoblastoma (HB). In the present study, the effect of LASS2 on the proliferation, apoptosis and cell cycle of HepG2 HB cells was assessed, and the underlying mechanisms were investigated. The human LASS2 coding sequence was inserted into an adenovirus vector and transduced into HepG2 cells. It was determined that the overexpression of LASS2 inhibited HepG2 cell viability and proliferation, as determined by cell counting kit-8 and colony formation assays, and induced apoptosis by increasing reactive oxygen species, reducing mitochondrial membrane potential and inducing intracellular Ca 2+ overload. In addition, the overexpression of LASS2 induced G 0 /G 1 cell cycle arrest through modulating the expression of cell cycle regulatory proteins, including p27, cyclin D1 and cyclin‑dependent kinase 4. Immunofluorescence was used to determine that nuclear factor (NF)-κB p-p65 was primarily expressed in the cytoplasm rather than in the nucleus; western blot analysis demonstrated that LASS2 downregulated the expression of NF-κB p-p65 relative to its inactive form in HepG2 cells. These findings suggest that LASS2 inhibits proliferation and induces apoptosis in HepG2 HB cells through the mitochondrial apoptotic, NF-κB and cell cycle signaling pathways.