# Role of histone demethylase JMJD1A in the DNA damage response of prostate cancer cells

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $353,419

## Abstract

ABSTRACT
PCa is the most common malignancy in American men. Therapies for advanced PCa include androgen
deprivation therapy (ADT), chemotherapy and radiotherapy, all of which can induce the DNA damage. Thus
the DNA damage response and expression of DNA repair genes are key factors in determining outcome of
genotoxic therapies for PCa. We have identified a pathway in which the histone demethylase JMJD1A
undergoes a non-canonical ubiquitination by the E3 ubiquitin ligase HUWE1, which in turn enhances JMJD1A
co-activation of androgen receptor and c-Myc transcription factors. Here, we will test the hypothesis that the
non-canonical ubiquitination of JMJD1A regulates expression of DNA repair genes through AR and c-Myc, and
promotes growth and survival of PCa cells under ionizing radiation (IR) and androgen deprivation conditions.
Aim one will assess JMJD1A mechanisms in regulating AR and c-Myc transcriptional activity. Aim two will
investigate JMJD1A function in DNA damage responses after IR and androgen deprivation in vitro. Aim three
will evaluate JMJD1A function in the response of xenografted prostate tumors to castration and IR. Finally, in
Aim four, we will investigate the aberrant expression of factors comprising HUWE1/JMJD1A/DNA repair gene
pathway in a human PCa tissue microarray (TMA). Our proposed studies should define a new pathway,
including JMJDJ1A and its targets and regulators, that governs PCa responses to ADT and radiotherapy. If
successful, this work may identify new therapeutic targets or markers for anti-PCa therapy.

## Key facts

- **NIH application ID:** 9980296
- **Project number:** 5R01CA207118-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jianfei Qi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,419
- **Award type:** 5
- **Project period:** 2016-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980296

## Citation

> US National Institutes of Health, RePORTER application 9980296, Role of histone demethylase JMJD1A in the DNA damage response of prostate cancer cells (5R01CA207118-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9980296. Licensed CC0.

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