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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
RUVBL1 is an amplified epigenetic factor promoting proliferation and inhibiting differentiation program in head and
Derrick Lin1, Brian Lin2, Haymanti Bhanot3
1Massachusetts Eye and Ear Infirmary, Harvard Medical School, United States; Massachusetts General Hospital Cancer Center, United States.
Abstract:
Mutations in histone modifying enzymes and histone variants were identified in multiple cancers in The Cancer Genome Atlas (TCGA) studies. However, very little progress and understanding has been made in identifying the contribution of epigenetic factors in head and neck squamous cell carcinoma (HNSCC). Here, we report the identification of RUVBL1 (TIP49a), a component of the TIP60 histone modifying complex as being amplified and overexpressed in HNSCC. RUVBL1 plays a key role in incorporating histone variant H2AZ in chromatin thereby regulating transcription of key genes involved in differentiation, cancer cell proliferation and invasion. H2AZ is also overexpressed in HNSCC tumors thereby regulating RUVBL1/H2AZ dependent transcriptional programs. Patient data analysis of multiple cohorts including TCGA and single cell HNSCC data indicated RUVBL1 overexpression as a poor prognostic marker and predicts poor survival. In vitro experiments indicate a pro-proliferative role for RUVBL1/H2AZ in HNSCC cells. RUVBL1 inversely correlates with differentiation program and positively correlates with oncogenic programs, making it a key contributor to tumorigenesis and a vulnerable therapeutic target in HNSCC patients.
Insights
RUVBL1, a histone modifier, is amplified and overexpressed in head and neck squamous cell carcinoma (HNSCC). Its overexpression indicates poor prognosis and promotes cancer cell proliferation, highlighting it as a therapeutic target.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Epigenetic alterations, including histone modifications, are implicated in various cancers.
- Understanding the role of epigenetic factors in head and neck squamous cell carcinoma (HNSCC) remains limited.
Purpose of the Study:
- To identify epigenetic factors contributing to HNSCC development.
- To investigate the role of RUVBL1 and H2AZ in HNSCC pathogenesis.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) and single-cell HNSCC data.
- In vitro experiments to assess the functional role of RUVBL1/H2AZ.
Main Results:
- RUVBL1 (TIP49a), a component of the TIP60 complex, is amplified and overexpressed in HNSCC.
- RUVBL1 and histone variant H2AZ are co-overexpressed, regulating key oncogenic transcriptional programs.
- RUVBL1 overexpression is a poor prognostic marker, predicting reduced survival in HNSCC patients.
- In vitro studies confirm a pro-proliferative role for RUVBL1/H2AZ in HNSCC cells.
Conclusions:
- RUVBL1/H2AZ axis plays a critical role in HNSCC tumorigenesis by promoting proliferation and invasion.
- RUVBL1 is inversely correlated with differentiation and positively correlated with oncogenic programs in HNSCC.
- RUVBL1 represents a potential therapeutic target for HNSCC treatment.
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