Comprehensive pan-cancer analysis of RIOK2 reveals its prognostic significance and oncogenic role in hepatocellular carcinoma

RIOK2 (right open reading frame kinase 2), a member of the atypical RIO kinase family, is involved in ribosome biogenesis, rRNA processing, and cell cycle regulation. However, the expression pattern, clinical relevance, and biological function of RIOK2 in human cancers remain unclear. We performed a pan-cancer analysis of RIOK2 using multiple public databases, including TCGA, GTEx, HPA, TIMER, TISIDB, GSCA, LinkedOmics, and TISCH. The expression profiles, clinical characteristics, survival outcomes, immune-related features, genomic alterations, and DNA methylation patterns associated with RIOK2 were systematically analyzed. In addition, siRNA-mediated RIOK2 knockdown was performed in HepG2 and Huh7 hepatocellular carcinoma cells, followed by CCK-8, colony formation, cell cycle, and apoptosis assays to evaluate its biological effects. RIOK2 expression was dysregulated in multiple cancer types and was associated with clinical characteristics and survival outcomes in several malignancies. In hepatocellular carcinoma (LIHC), increased RIOK2 expression was associated with poor prognosis and showed correlations with immune-related molecular features. Functional enrichment analysis revealed that RIOK2-related genes were mainly involved in ribosome biogenesis, rRNA processing, RNA metabolism, and translation-related pathways. Single-cell transcriptomic analysis showed that RIOK2 was preferentially expressed in malignant LIHC cells. Furthermore, in vitro experiments demonstrated that RIOK2 expression was increased in hepatocellular carcinoma cells, while RIOK2 knockdown inhibited cell proliferation, promoted apoptosis, and affected cell cycle progression. Our findings characterize the expression landscape and clinical relevance of RIOK2 across human cancers and suggest that RIOK2 may contribute to hepatocellular carcinoma progression. RIOK2 may represent a potential molecular candidate for further investigation in LIHC.