Inhibition of FAM114A1 Suppresses Hepatocellular Carcinoma by Targeting AKT1 Signaling.

Abstract

Objective: Hepatocellular carcinoma (HCC) poses a significant challenge owing to its aggressive nature and elevated mortality rates. Understanding the role of novel therapeutic targets is essential. Although linked to several diseases, the role of the family with sequence similarity 114 member A1 (FAM114A1) in HCC remains unclear.

Methods: Utilizing UALCAN and GEPIA databases, the expression of FAM114A1 in HCC tissues was examined, alongside exploring its correlation with AKT1. FAM114A1 expression in HCC cells was assessed through qRT-PCR experiments. Following lentiviral transduction to suppress FAM114A1 expression in these cells, subsequent analyses involved MTT assays, scratch assays, Transwell analysis, and flow cytometry to investigate the impact of FAM114A1 depletion on cell proliferation, migration, apoptosis, and cell cycle dynamics. Furthermore, Western blot analysis assessed EMT-related proteins (Snail, MMP2, MMP9) and AKT1 expression. Overexpression of AKT1 in HCC cells was performed, and its effects on cell proliferation and migration were assessed using MTT assays and Transwell analysis.

Results: Elevated FAM114A1 expression was observed in HCC tissues and cells. FAM114A1 suppression reduced cell proliferation and migration by modulating AKT1. FAM114A1 knockdown promoted apoptosis, arrested the cell cycle, and inhibited EMT.

Conclusions: Overall, our study suggests that FAM114A1 plays a role in HCC cell proliferation and migration, involving the modulation of AKT1 expression. Furthermore, FAM114A1 impacts apoptosis, cell cycle, and EMT, contributing to HCC development. These findings highlight FAM114A1 as a potential novel therapeutic target for HCC treatment.