Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignant tumors worldwide with poor clinical outcomes and high mortality rates, highlighting the pressing need to identify reliable biomarkers. Nucleolar protein 11 (NOL11), as an essential element for ribosomal biosynthesis, has been implicated in the development and progression of various diseases. However, the potential role of NOL11 in HCC remains elusive. METHODS: The expression level of NOL11 was investigated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the correlation between NOL11 and the clinical characteristics was analyzed. Furthermore, spatial-temporal expression patterns of NOL11 were delineated based on single-cell and spatial transcriptomics. Cox regression and ROC analyses were performed to evaluate the prognostic and diagnostic value of NOL11. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were conducted to elucidate the functional pathways and potential mechanisms associated with NOL11. The association of NOL11 with immune infiltration was also explored using single-sample Gene Set Enrichment Analysis (ssGSEA). The integrated bioinformatics analysis was utilized to identify the drug sensitivity, and further drug validation was employed via molecular docking. Finally, the biological function of NOL11 was validated through in vitro experiments. RESULTS: The expression of NOL11 was significantly upregulated in HCC, especially in tumor cells. Elevated NOL11 levels closely correlated with worse clinicopathological features, poor prognosis, and immune infiltration. Functional enrichment analysis revealed NOL11's potential involvement in multiple cancer-associated signaling pathways, including the cell cycle, DNA replication, and cell metabolism. Furthermore, we found that common chemotherapy drugs, such as gemcitabine, trametinib, and paclitaxel were sensitive to the expression of NOL11 and exhibited a strong molecular combination with NOL11. Lastly, NOL11 knockdown suppressed the proliferation, migration, and invasion of HCC cells. CONCLUSION: Our findings suggest that NOL11 is a promising diagnostic and prognostic biomarker for HCC, providing new insights into the treatment decisions for HCC patients.