Syntaxin 1 A knockdown suppresses hepatocellular carcinoma cell viability and invasion but induces apoptosis primarily through the AKT pathway

Syntaxin 1 A (STX1A) was recently shown to regulate the progression of several cancers. However, the role of STX1A in hepatocellular carcinoma (HCC) remains unclear. We examined how STX1A affects HCC cell behavior and its relationship to the AKT and ERK pathways.

The clinical implications of STX1A in HCC patients were analyzed using the GEPIA database. STX1A siRNA was transfected into two HCC cell lines (Huh-7 and MHCC-97H), after which cell viability, apoptosis, invasion, and western blotting were performed. SC79 was subsequently used to activate the AKT pathway in HCC cells with or without STX1A siRNA transfection.

GEPIA analysis showed that STX1A was more highly expressed in HCC and that higher STX1A expression was associated with shorter overall survival and disease-free survival, and its expression varied among HCC patients with different tumor stages. STX1A knockdown impaired the viability and invasive capacity of Huh-7 and MHCC-97H cells while promoting apoptosis. In HCC tissues, higher STX1A expression was accompanied by increased expression of AKT1, ERK1, and ERK2. However, STX1A knockdown downregulated only p-AKT expression in Huh-7 and MHCC-97H cells. Notably, SC79-induced AKT pathway activation promoted cell viability and invasion but reduced apoptosis in Huh-7 and MHCC-97H cells; in particular, SC79 attenuated the effects of STX1A knockdown on Huh-7 and MHCC-97H cellular functions.

STX1A knockdown suppresses HCC cell viability and invasion but induces apoptosis, which is associated with the suppression of the AKT pathway; however, further in vivo studies are needed to validate the antitumor effects of STX1A knockdown.