promotes progression of hepatocellular carcinoma through Wnt/β-catenin signaling.

BACKGROUND

Hepatocellular carcinoma is a widespread cancer worldwide, ranking as the fifth most frequent cancer and the fourth leading cause of cancer-related deaths. According to comprehensive research, , a phosphorylated kinase, has been discovered to play a crucial role in promoting tumor development. However, the prognostic significance and influence of on hepatocellular carcinoma tumor cells and the immune microenvironment remain unexplored, warranting further investigation. The aim of this study was to investigate the role of in promoting the development of hepatocellular carcinoma.

METHODS

The present study utilized The Cancer Genome Atlas (TCGA) database and other databases as training sets to examine the expression of and its prognostic significance. The findings were subsequently validated through cell proliferation assays and cell colony assays. Gene set enrichment analysis (GSEA) was employed to investigate the tumor-related biological processes associated with in hepatocellular carcinoma, while the relationship between expression and Wnt/β-catenin signaling pathway was analyzed via TCGA dataset analysis. Western blotting and immunofluorescence assays were used to confirm the experimental results.

RESULTS

showed higher expression levels in tumor tissues than in normal tissues. Alpha fetoprotein (AFP), T stage, pathological stage, and histological grade were significantly associated with expression. High expression correlated with worse overall survival (OS) [hazard ratio (HR) =1.62, 95% confidence interval (CI): 1.14-2.29, P=0.007], progression-free survival (PFS) (HR =1.88, 95% CI: 1.40-2.52, P<0.001) and disease specific survival (DSS) (HR =1.86, 95% CI: 1.18-2.93, P=0.007) in the training and validation sets. Both univariate and multivariate analyses showed that was an independent prognostic factor. GSEA showed that was significantly enriched in tumor-related biological processes. induced the activation of β-catenin signaling, resulting in sustained tumor growth. Methyl thiazolyl tetrazolium (MTT) and colony formation assays demonstrated that could promote hepatocellular carcinoma progression. Furthermore, showed a significant association with β-catenin in the Wnt pathway.

CONCLUSIONS

represents an independent prognostic factor in hepatocellular carcinoma and can promote cancer progression via the β-catenin signaling pathway.