Promotion of hepatocellular carcinoma stemness and progression by abnormal spindle-like microcephaly-associated protein via the Wnt/β-catenin pathway

Background: Cancer stem cells (CSCs) play a crucial role in tumor recurrence and metastasis, which are the primary causes of death in patients with hepatocellular carcinoma (HCC). Currently, no drug effectively blocks the recurrence and metastasis of liver cancer, leading to a poor prognosis for patients. To enhance treatment outcomes, there is an urgent need to investigate the molecular mechanisms behind the recurrence and progression of liver cancer, with the aim of identifying effective therapeutic targets. Targeting HCC stemness can improve the prognosis of patients with HCC. Abnormal spindle-like microcephaly-associated protein (ASPM) plays a pivotal role in regulating neurogenesis and brain size, which is a centrosome protein. ASPM has been implicated in tumorigenesis and tumor progression, but its regulatory role in HCC stemness is not well understood. This study aims to investigate the role of ASPM in liver cancer stemness and elucidate its potential molecular mechanisms. Methods: Bioinformatics analysis was used to study the expression of ASPM and its clinical significance in HCC. In vitro and in vivo assays were conducted to clarify the impact of ASPM knockdown on HCC cell stemness. The correlation between ASPM and the Wnt/β-catenin pathway was examined through analysis of online databases and in vitro experiments. Results: The bioinformatics analysis revealed significant upregulation of ASPM was significantly upregulated in HCC samples, with expression correlating with poor prognosis. In vitro experimental data confirmed elevated ASPM expression in HCC cells compared to normal hepatocytes. Knockdown of ASPM suppressed HCC cell growth, clone formation, spheroid formation, migration, invasion, and the expression of CSC markers CD133 and CD44. This also inhibited the activation of the Wnt/β-catenin pathway. Reactivation of this pathway partially reversed the biological changes induced by ASPM knockdown in HCC cells. Additionally, in vivo data demonstrated that ASPM downregulation reduced the size and weight of xenografts in BALB/c mice, along with decreased expression of CSC markers. Conclusions: These findings suggest that ASPM promotes HCC stemness and progression through the Wnt/β-catenin pathway. Targeting ASPM or the Wnt/β-catenin pathway may be a promising strategy to prevent HCC chemoresistance and recurrence, ultimately improving patient prognosis.