The reprogramming of lipid metabolism serves an important role in occurrence and development of
liver cancer.
Fatty acid hydroxylase domain containing 2 (FAXDC2) is a
hydroxylase involved in the synthesis of
cholesterol and
sphingomyelin and downregulated in various types of
cancer. There are no reports on the relationship between FAXDC2 and liver
carcinogenesis. The present study used multiple portals and publicly available tools to explore its correlation with
liver cancer. The results showed that the expression of FAXDC2 decreased in
liver cancer and the methylation level near the promoter increased. Patients with
liver cancer and with low expression of FAXDC2 had a poor prognosis. Gain of function and loss of function strategies were performed to evaluate its roles in
liver cancer cells.
CCK-8 assay showed that overexpression of FAXDC2 inhibited the viability of
liver cancer cells (HepG2). Flow cytometry analysis indicated that HepG2 cells with overexpressing FAXDC2 showed an S phase arrest, associated with
cyclin-dependent kinase 2 decreased. Transwell experiments showed that increasing FAXDC2 inhibited HepG2 cell invasion ability, accompanied by the upregulation of
E-cadherin. Notably, knockdown of FAXDC2 had no significant effect on cell cycle and invasion functions. Based on the cBioPortal platform, FAXDC2 was predicted to closely correlate to the ERK signal in
tumorigenesis. Western blotting results showed that overexpression of FAXDC2 decreased the phosphorylation level of ERK in
liver cancer cells. The present study first identified FAXDC2 as a
liver cancer suppressor, which might inhibit the proliferation and invasion of
liver cancer cells through the mechanism associated with ERK signaling. The present study provided a possible new target for the diagnosis and treatment of
liver cancer.