Abstract

Liver cancer, a primary malignancy of liver cells, exhibits high morbidity and mortality. Family with sequence similarity 64, member A (FAM64A) acts as an oncogene and modulates tumor progression in multiple cancers. However, the specific role of FAM64A in liver cancer development remains poorly elucidated. Thus, this work uncovered the action of FAM64A on liver cancer pathogenesis and cancer immunity and reveals the underlying mechanism. In this study, the FAM64A expression in liver cancer and its association with the overall survival were investigated using bioinformatics analysis. Tumor tissues and adjacent normal tissues were obtained from 64 liver cancer cases. Cell viability, invasion, and angiogenesis were assessed by CCK-8 method, Transwell invasion assay, and tube formation assay, respectively. The secretion levels of IFN-γ, IL-2, IL-10 and TGF-β were tested utilizing the ELISA assay. A xenograft tumor was created to monitor tumor growth in vivo . Results revealed that FAM64A expression was elevated in liver cancer. Clinically, high FAM64A levels correlated with shorter overall survival. Silencing of FAM64A restricted the malignant phenotypes of liver cancer cells, including proliferation, invasion, angiogenesis and immune escape. Furthermore, FAM64A knockdown restricted the activation of the VEGFA/AKT signaling. Conversely, VEGFA overexpression offset the above influences of FAM64A on liver cancer cells. Moreover, silenced FAM64A suppressed tumor growth, decreased CD31 and PD-L1 levels, increased CD8 and IFN-γ level, and reduced activation of the VEGFA/AKT signaling. Taken together, FAM64A is up-regulated in liver cancer and closely correlated with poor prognosis. Silenced FAM64A restrained proliferation ability, invasion capacity, angiogenesis and immune escape of liver cancer cells through inactivating the VEGFA/AKT signaling. FAM64A may be a valuable candidate target for liver cancer therapy.