[ATPase H⁺ transporter expression with prognosis in hepatocellular carcinoma]

Objective: To investigate the expression level of ATPase H⁺ transporting accessory protein 1 (ATP6AP1) in hepatocellular carcinoma (HCC) lines and its effect on cell proliferation and migration, providing a new target for the treatment of HCC. Methods: Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the differential expression of ATP6AP1 in normal hepatocyte line L02 and hepatocellular carcinoma line HepG2. An ATP6AP1 knockdown group (KD group) and a negative control group (NC group) were constructed by lentiviral infection. The proliferation and migration abilities were detected by CCK8 cell proliferation and cell scratch assay between the two groups. Independent samples t-test was used to analyze the differences between groups. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA) databases using Kaplan-Meier Plotter, UALCAN, and GEPIA to explore the differential expression of ATP6AP1 in HCC patients and its impact on prognosis. Results: Bioinformatics results showed that the expression level of ATP6AP1 was significantly higher in HCC tissues than that in normal liver tissues (P<0.05). Functional enrichment analysis indicated that ATP6AP1 regulated lysosomal function, intracellular acidification, and the immune microenvironment in HCC progression. RT-PCR results showed that ATP6AP1 mRNA expression was significantly higher in HepG2 liver cancer cells than that in normal hepatocytes L02 (P<0.05). The relative expression level of ATP6AP1 mRNA was significantly lower in the KD group (0.18±0.01) than that in the NC group (1.00±0.08) (P<0.001). CCK assays showed that the profileration capacity was significantly higher in KD group than that in the NC group from day 3 to day 5 (P<0.05), with a significant time-effect relationship (P<0.001). Cell scratch assay results showed that the migration rate was significantly higher in the NC group than that of the KD group over time, with a slower scratch repair rate. Conclusion: High expression of ATP6AP1 plays a pro-cancerous role in HCC progression and may serve as a potential biomarker for predicting prognosis and a potential therapeutic target.Therefore, further validation of its mechanism of action in animal models and clinical samples is needed in the future.