# HULLK, a novel lncRNA that functions as a targetable oncogene in PCa

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $410,710

## Abstract

Abstract
There remains a critical need for more effective therapies for prostate cancer and for castration resistant prostate
cancer. While localized prostate cancer (PCa) has a favorable prognosis, castration-resistant prostate cancer
(CRPC) remains incurable. The failure of current therapies demonstrates a need for new approaches, and
exposes an incomplete understanding of the underlying mechanisms that drive PCa to CRPC. Long noncoding
RNAs (lncRNAs) have been underappreciated as critical regulatory elements of many cellular biological
processes relevant to cancer development and progression. These IncRNAs may be targets for potent new
therapies to combat PCa progression. We have recently published the discovery of a novel lncRNA that acts as
an oncogene in PCa. This unannotated lncRNA is dramatically upregulated by androgen in a dose-dependent
manner and the hormone-induced increase is completely blocked by the anti-androgen enzalutamide. We have
named this lncRNA “HULLK” for Hormone-Upregulated lncRNA within LCK. HULLK transcripts are expressed in
patient tissue and there is a significant positive correlation between HULLK expression and high-grade PCa in
three independent cohorts: The Cancer Genome Atlas, the University of Virginia, and the University of Texas
Southwestern. Important for potential therapeutics, shRNAs specifically targeting HULLK significantly decreased
PCa cell growth, including CRPC cells expressing the ligand independent ARv7. These data lead to the
hypothesis that HULLK is a novel lncRNA that functions as a targetable oncogene in PCa. In this proposal we
will test HULLK as a driver of PCa in patient-derived xenograft in vivo models, provide proof-of-concept
therapeutic targeting of HULLK, and identify HULLK binding partners, which is the critical first step for
determining the molecular mechanism of HULLK. This proposal integrates innovative conceptual, technical, and
translational elements to uncover the molecular mechanisms through which HULLK drives PCa and to evaluate
HULLK as a potential therapeutic target in this devastating disease.

## Key facts

- **NIH application ID:** 10198408
- **Project number:** 1R21CA259716-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Daniel G Gioeli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,710
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198408

## Citation

> US National Institutes of Health, RePORTER application 10198408, HULLK, a novel lncRNA that functions as a targetable oncogene in PCa (1R21CA259716-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10198408. Licensed CC0.

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