{"title":"Profiling of RUVBL2-Induced Transcriptome Alterations Highlights a Critical Role for Chromatin Remodeling in Ovarian Cancer","authors":"Renhao Xue, Yingjie Wang, Xiaomei Luo, Hao Zhang, Dongcheng Guan, Shuo Shi, Yu Wang","doi":"10.1002/biof.70041","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Cancerous transcriptome alterations in carcinoma cells could be originated from either genetic copy number changes or epigenetic reprogramming. Ovarian cancer (OV) is the most malignant gynecologic tumor, known for high aneuploidy with robust copy number alterations. However, low aneuploidy ovarian tumors are also frequently found, indicating an essential contribution of epigenetic factors during tumorigenesis and cancer development. Chromatin remodeling modulates the transcriptome epigenetically in a variety of cancer types, but its role in OV is still unclear. Hence, we investigated a cohort of 102 OV patients, analyzed transcriptomic and clinical data from public databases, and performed cellular experiments. We found that RUVBL2, a subunit of the INO80 complex, functions as the key oncogenic chromatin remodeler in OV. RUVBL2 is upregulated in tumors, particularly in low-aneuploidy cases, and is associated with poor prognosis. RUVBL2 drives nucleosome dynamics and elevates chromatin accessibility selectively at promoter regions. The landscape of RUVBL2-dependent modulation of chromatin accessibility and the transcriptome exhibits activation of various transcription factors, especially the AP-1 family, and upregulation of a series of key genes, including <i>CDKN3</i>, <i>MYBL2</i>, and <i>ZNF144</i>, resulting in mediation of cell cycle and Hippo signaling pathway to promote DNA synthesis and cell proliferation. Hence, RUVBL2-dependent chromatin remodeling plays a key role in oncogenic reprogramming of the transcriptome in OV. These findings provide novel insights into the molecular etiology of OV and disclose potential biomarkers and drug targets.</p>\n </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 4","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioFactors","FirstCategoryId":"99","ListUrlMain":"https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.70041","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cancerous transcriptome alterations in carcinoma cells could be originated from either genetic copy number changes or epigenetic reprogramming. Ovarian cancer (OV) is the most malignant gynecologic tumor, known for high aneuploidy with robust copy number alterations. However, low aneuploidy ovarian tumors are also frequently found, indicating an essential contribution of epigenetic factors during tumorigenesis and cancer development. Chromatin remodeling modulates the transcriptome epigenetically in a variety of cancer types, but its role in OV is still unclear. Hence, we investigated a cohort of 102 OV patients, analyzed transcriptomic and clinical data from public databases, and performed cellular experiments. We found that RUVBL2, a subunit of the INO80 complex, functions as the key oncogenic chromatin remodeler in OV. RUVBL2 is upregulated in tumors, particularly in low-aneuploidy cases, and is associated with poor prognosis. RUVBL2 drives nucleosome dynamics and elevates chromatin accessibility selectively at promoter regions. The landscape of RUVBL2-dependent modulation of chromatin accessibility and the transcriptome exhibits activation of various transcription factors, especially the AP-1 family, and upregulation of a series of key genes, including CDKN3, MYBL2, and ZNF144, resulting in mediation of cell cycle and Hippo signaling pathway to promote DNA synthesis and cell proliferation. Hence, RUVBL2-dependent chromatin remodeling plays a key role in oncogenic reprogramming of the transcriptome in OV. These findings provide novel insights into the molecular etiology of OV and disclose potential biomarkers and drug targets.
期刊介绍:
BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease.
The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements.
In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.