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Hepatocellular carcinoma (HCC) continues to play a substantial role in cancer-related morbidity and mortality, largely owing to its pronounced tumor heterogeneity and propensity for recurrence. This underscores the pressing need for in-depth examination of its highly malignant mechanisms. Annexin A5 (ANXA5), recognized as a hallmark tumor protein, has emerged as a focal point of interest because of its ambiguous function and mechanism in HCC prognosis. This study aimed to provide a comprehensive understanding of the role of ANXA5 in the malignant progression of human HCC cells by employing an integrative approach that combines conventional experimental methods with RNA sequencing. Differences in ANXA5 expression between HCC tissues and corresponding nontumor tissues were evaluated using immunofluorescence (n = 25). Correlation analysis was subsequently performed to assess the association between ANXA5 expression and clinicopathological features (n = 65). The role of ANXA5 in human HCC cell lines with ANXA5 gene knockout and overexpression was explored in vitro using migration and invasion assays and Ki-67 indices and in vivo based on node mice xenograft model. A tube formation assay using human umbilical vein endothelial cells (HUVECs) was conducted to demonstrate the angiogenic effects of ANXA5 in HCC. Single-cell and bulk RNA sequencing was used to further investigate the underlying mechanisms involved. This study revealed that ANXA5 is highly expressed in patients with HCC and correlates with poor prognosis. Assays for migration, invasion, and proliferation based on ANXA5 gene knockout and overexpression systems in human HCC cell lines have demonstrated that ANXA5 enhances HCC malignancy in vitro and in vivo. Tube formation assays of HUVECs indicated that ANXA5 facilitates angiogenesis and recruits endothelial cells to HCC cells. Single-cell and bulk RNA sequencing data analysis further confirmed that ANXA5 expression in HCC is associated with hepatocyte metabolism, immune response activation, and various oncogenic signaling pathways. This study revealed a meaningful association between elevated ANXA5 expression in tumor tissues and an unfavorable prognosis in patients with HCC. In addition, ANXA5 promotes HCC malignancy by promoting invasion and angiogenesis. Thus, ANXA5 has emerged as a promising therapeutic target for HCC and has the potential to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression. [ABSTRACT FROM AUTHOR]