{"title":"RIOK1: A Novel Oncogenic Driver in Hepatocellular Carcinoma.","authors":"Chunyan Ruan, Tianyu Shang, Sijia Zhang, Wenhong Ru, Yuefeng Yang, Yi Shen","doi":"10.1002/cam4.70597","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Our findings suggest that RIOK1 is a novel oncogenic driver that may serve as a potential diagnostic and therapeutic target for HCC.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":"e70597"},"PeriodicalIF":2.9000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cam4.70597","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.