# Role of UHRF1 in osteosarcoma and its relationship to RB

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $408,942

## Abstract

Metastasis remains the most significant fatal complication in the treatment of osteosarcoma. Among the
patients who develop metastasis, less than 1 in 5 survive. Genetic alterations at the RB transcriptional
corepressor 1 (RB1) gene have been associated with increased mortality, metastasis and poor response to
chemotherapy in osteosarcoma. However, the precise mechanism through which this occurs remains to be
elucidated. Studies in our laboratory identified UHRF1 (Ubiquitin-like, containing PHD and RING Finger
domains 1), as a gene that is upregulated and its protein overexpressed in osteosarcoma. UHRF1 is a
multifunctional protein involved in epigenetic regulation that has been shown to interact with RB. Further, the
RB/E2F pathway directly regulates UHRF1 expression. Our data indicates that targeting UHRF1
overexpression dramatically increases survival in mice bearing osteosarcoma tumors and reduces the rate and
number of metastases. The goal of this proposal is to determine the mechanism(s) through which UHRF1
contributes to tumor progression to help design novel therapeutic interventions for the treatment of
osteosarcoma. These studies also evaluate whether UHRF1 is a valid target for most osteosarcomas or only
those bearing RB1 mutations. For this, we will define the role of UHRF1 in osteosarcoma pathogenesis and
progression, focusing on its relationship with RB1 and define the roles of each of the UHRF1 functional
domains in the UHRF1-associated migration and invasion in osteosarcoma. This proposal tests the hypothesis
that gene expression alterations driven by UHRF1 underlie tumor progression and poor survival in
osteosarcoma. Successful completion of this work is likely to directly influence the development of UHRF1
inhibitors relevant for therapeutic intervention for osteosarcoma and other cancers with UHRF1
overexpression.

## Key facts

- **NIH application ID:** 9935015
- **Project number:** 5R01CA229696-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Claudia Andrea Benavente
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,942
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935015

## Citation

> US National Institutes of Health, RePORTER application 9935015, Role of UHRF1 in osteosarcoma and its relationship to RB (5R01CA229696-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9935015. Licensed CC0.

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