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Profiling of RUVBL2-Induced Transcriptome Alterations Highlights a Critical Role for Chromatin Remodeling in Ovarian
Renhao Xue1,2, Yingjie Wang1, Xiaomei Luo1,2
1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Biofactors (Oxford, England)
|August 4, 2025
Summary
RUVBL2, a chromatin remodeler, is upregulated in ovarian cancer (OV), especially in low-aneuploidy tumors. This oncogenic protein drives tumor progression by altering gene expression, offering potential biomarkers and drug targets for ovarian cancer.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Ovarian cancer (OV) exhibits significant transcriptome alterations driven by genetic or epigenetic factors.
- While aneuploidy is common in OV, low-aneuploidy tumors suggest a crucial role for epigenetic reprogramming.
- The specific role of chromatin remodeling in OV tumorigenesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of chromatin remodeling in ovarian cancer.
- To identify key epigenetic regulators involved in OV development and progression.
- To explore potential therapeutic targets and biomarkers for ovarian cancer.
Main Methods:
- Analysis of transcriptomic and clinical data from 102 ovarian cancer patients.
- Utilized public databases for data mining.
- Conducted cellular experiments to validate findings.
Main Results:
- Identified RUVBL2 (a subunit of the INO80 complex) as a key oncogenic chromatin remodeler in OV.
- Found RUVBL2 upregulation in tumors, particularly in low-aneuploidy cases, correlating with poor prognosis.
- Demonstrated RUVBL2's role in modulating nucleosome dynamics, increasing chromatin accessibility, and activating transcription factors like AP-1, leading to cell cycle and Hippo pathway dysregulation.
Conclusions:
- RUVBL2-dependent chromatin remodeling is a critical driver of oncogenic transcriptome reprogramming in ovarian cancer.
- RUVBL2 plays a significant role in promoting DNA synthesis and cell proliferation in OV.
- These findings highlight RUVBL2 as a potential biomarker and therapeutic target for ovarian cancer.
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