# Role of NF90 in Prostate Cancer

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $361,425

## Abstract

Summary
Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer and the third leading
cause of cancer deaths in American men. While early-stage PCa can be effectively treated with
surgery and radiation therapy, metastatic prostate cancer remains a challenge and androgen
deprivation therapy (ADT) is the mainstay treatment. Although a majority of advanced PCa
initially responds well to ADT, they ultimately develop resistance and become castration-
resistant, called CRPC. CRPC tumors no longer need androgen to grow but often remain
dependent on an aberrantly active androgen receptor (AR). Understanding the mechanisms to
this androgen-independent AR activation may shed significant light on effective strategies to
eradicate CRPC. EZH2 is an enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2)
that catalyzes histone H3 lysine 27 trimethylation to suppress gene expression, a role that can
be effectively targeted by enzymatic EZH2 inhibitors. Recent evidence suggests that EZH2 may
have PRC2-independent roles in activating gene expression. However, critical gaps remain as
to what the target genes are, how EZH2 activates them, and how they work in concert with the
epigenetic roles of EZH2 to promote CRPC. Our preliminary results showed that AR is a direct
target of EZH2-mediated transcriptional activation. This activation is likely mediated by EZH2-
interacting co-activator NF90. Our preliminary data further showed that NF90 is up-regulated in
CRPC and exhibits oncogenic functions. The roles of NF90, however, have never been studied
in PCa. We hypothesize that NF90 cooperates with EZH2 in transcriptional activation of AR and
promotes CRPC progression. To test these hypotheses, three Specific Aims are proposed. Aim
1 will determine how NF90 interacts with EZH2 protein to mediate AR gene transcription. Aim 2
will determine how NF90 regulates EZH2 chromatin recruitment and target gene activation
using ChIP-seq and RNA-seq assays, characterize downstream genes/pathways of NF90, and
examine the expression of NF90 in primary PCa tissues to determine its correlation with EZH2
expression and clinical outcomes. Lastly, Aim 3 will characterize the roles of NF90 in prostate
cancer in vitro and in vivo and, most importantly, test the efficacy of a new combinatorial
therapeutic approach that simultaneously blocks the dual roles of EZH2 using enzymatic EZH2
inhibitor GSK126 and AR antagonist enzalutamide in PCa patient-derived xenograft (PDX)
models.

## Key facts

- **NIH application ID:** 9999528
- **Project number:** 5R01CA227918-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jindan Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,425
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999528

## Citation

> US National Institutes of Health, RePORTER application 9999528, Role of NF90 in Prostate Cancer (5R01CA227918-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999528. Licensed CC0.

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