RIOK1: A Novel Oncogenic Driver in Hepatocellular Carcinoma

ABSTRACT Background Hepatocellular carcinoma (HCC) is one of the most common and highly lethal cancers worldwide. RIO kinase 1 (RIOK1), a protein kinase/ATPase that plays a key role in regulating translation and ribosome assembly, is associated with a variety of malignant tumors. However, the role of RIOK1 in HCC remains largely unknown. Methods Changes in RIOK1 expression in HCC and patient prognosis were evaluated using HCC tissues and public databases. The functional role of RIOK1 in HCC was analyzed by RTCA assay, clonogenic assay, and flow cytometry in vitro, and by mouse tumor xenograft model in vivo. Potential mechanism studies were performed using multi‐omics analysis, public database screening, and qRT‐PCR assay. Results In this study, we found that RIOK1 was elevated in HCC tissues and correlated with poor prognosis. Functional assays demonstrated that RIOK1 knockdown suppressed HCC cell proliferation, survival, and tumor growth in vivo, while RIOK1 overexpression enhanced these oncogenic phenotypes. Meanwhile, RIOK1 knockdown affected cell cycle progression and the expression of cyclin A2 and cyclin B1. Furthermore, integrated transcriptomic and proteomic analysis revealed that RIOK1 may promote HCC cell proliferation by affecting the cell cycle and DNA repair pathways. Moreover, we identified five potential effectors regulated by RIOK1: PMS1, SPDL1, RAD18, BARD1, and SMARCA5, which were highly expressed in HCC tissues and negatively correlated with the overall survival of HCC patients. Conclusion Our findings suggest that RIOK1 is a novel oncogenic driver that may serve as a potential diagnostic and therapeutic target for HCC.