Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. SEMA4F is an immune-related gene associated with HCC survival. As a transmembrane semaphorin, semaphorin 4F plays a key role in various biological processes. Recent studies have found that semaphorin 4F is closely related to cancer progression, but its role in HCC remains unclear. In this study, we aimed to investigate the function and related mechanisms of SEMA4F in HCC. METHODS: Public databases were used to analyze the expression and prognosis of SEMA4F in HCC. Overexpression/knockdown cell models were constructed via lentiviral transfection/siRNA technology. The function of SEMA4F was explored through in vitro cellular experiments. Transcriptome sequencing was employed to investigate its molecular mechanisms, and Western blot was used to validate the expression of pathway proteins. RESULTS: SEMA4F expression was elevated in tumor tissues of HCC patients and was associated with poor prognosis and shorter overall survival. In vitro analyses showed that SEMA4F overexpression promoted the proliferation, invasion, and migration of HCC cells, while SEMA4F knockdown led to the opposite phenotype. Furthermore, SEMA4F partially promoted HCC cell proliferation, migration, and invasion by activating the PI3K-Akt pathway; inhibition of this pathway significantly attenuated the pro‑proliferative, migratory, and invasive effects of SEMA4F. CONCLUSION: Our study reveals the function of SEMA4F in HCC. These findings suggest that SEMA4F is a potential prognostic biomarker for HCC and exerts pro‑cancer effects through activation of the PI3K-Akt pathway. These findings suggest SEMA4F as a potential therapeutic target, pending in vivo validation and clinical investigation.