Unveiling FGL1: a regulator of hepatocellular carcinoma proliferation and apoptosis via the PI3K/AKT/mTOR signaling pathway

Atezolizumab combined with bevacizumab represents the standard first‑line regimen for unresectable hepatocellular carcinoma (HCC). Previous reports indicated FGL1 is a vital secreted protein implicated in HCC progression and sorafenib resistance, yet its prognostic value and regulatory mechanism remain incompletely clarified. This study aims to explore the function of FGL1 in HCC cell proliferation and apoptosis, and further elucidate its underlying mechanism targeting the PI3K/AKT/mTOR signaling pathway. Bioinformatic analyses were performed based on public HCC datasets to evaluate FGL1 expression, clinical relevance and pathway enrichment. HCC cell lines were subjected to FGL1 knockdown and overexpression. CCK-8, flow cytometry and colony formation assays were used to detect cell proliferation, apoptosis and sorafenib responsiveness. Western blot was applied to measure the protein levels of key molecules within the PI3K/AKT/mTOR pathway. Rescue experiments were conducted to verify the causal relationship between FGL1 and the signaling cascade. Cox regression analysis was utilized to assess prognostic predictors. Bioinformatics results indicated that FGL1 expression was aberrantly altered in HCC and closely correlated with disease progression. Cellular experiments demonstrated that FGL1 knockdown accelerated HCC cell proliferation, suppressed cell apoptosis, whereas FGL1 overexpression exerted opposite effects. Mechanistically, FGL1 may negatively modulate the activation of the PI3K/AKT/mTOR pathway. Rescue experiments showed that the PI3K inhibitor BKM120 partially altered cellular phenotypes induced by FGL1 manipulation. Survival analysis revealed that altered FGL1 expression served as a potential prognostic indicator for HCC patients. FGL1 modulates proliferation and apoptosis of HCC cells, at least partially, via regulating the PI3K/AKT/mTOR signaling pathway. FGL1 could act as a promising biomarker for prognostic evaluation and a potential therapeutic target for hepatocellular carcinoma. Not applicable