ANP32A interacts with LDHA to modulate glycolysis and ferroptosis in hepatocellular carcinoma.

Acidic leucine-rich nuclear phosphoprotein 32A(ANP32A) is known to possess multi-functions and has been observed to exhibit different roles across various malignancies. Although the expression of ANP32A has been shown to correlate with metastatic spread and reduced survival in Hepatocellular carcinoma(HCC), the underlying mechanisms have not been fully elucidated. This study utilized univariate Cox regression, differential gene analysis, and WGCNA to identify ANP32A as closely associated with poor HCC prognosis. Our Co-IP results confirmed the interaction between ANP32A and LDHA. Additionally, silencing ANP32A inhibited HCC cell proliferation in vitro as well as in vivo, and altered glycolytic and ferroptotic pathways, with increased LDHA ubiquitination detected. These data suggested that ANP32A may play a role in HCC progression, positioning it as a highly attractive therapeutic target for advanced HCC. Silencing ANP32A augmented the susceptibility of HCC cells to ferroptosis and inhibited aerobic glycolysis, which may provide new avenues for combination therapies, offering potential for improved patient outcomes.