# Implication of a novel long noncoding RNA in therapy resistant prostate cancer with altered AR signaling

> **NIH NIH R21** · UNIVERSITY OF CENTRAL FLORIDA · 2020 · $166,296

## Abstract

PROJECT SUMMARY/ABSTRACT
Prostate cancer affects a significant number of men every year. The major challenge of prostate
cancer management is the development of therapy resistance. Since PCa growth depends on androgen
and androgen receptor (AR) functions, androgen deprivation therapy (ADT) and treatment with AR antagonists
are the mainstay of advanced PCa. Current therapies although initially effective a group of treatment
refractory tumor cells eventually emerges with a more aggressive phenotype which contributes to the
progression of incurable metastatic disease. There is a need for development of improved methods to
understand the biological basis for acquisition of drug resistance and identify novel targets for therapy.
Recently, microRNAs (miRNA) and long non-coding RNAs (lncRNA) as regulatory molecules for modulating
function of a diverse array of genes gained significant attention for their potential application as prognostic
markers and therapeutic targets. However, the mechanistic role of these regulatory RNAs and their
functional interdependence is not fully understood. Our preliminary studies on profiling of RNA transcripts
identified a negative correlation in expression between a tumor suppressor miRNA cluster and a novel
lncRNA in metastatic prostate cancer cells. A significant loss of expression of this lncRNA was noted
upon restored expression of the miRNA cluster in androgen refractory and therapy resistant prostate cancer
cells. The objective of the proposed study is to determine the functional relationship between these two
classes of non-coding RNAs (ncRNA) and the role of the lncRNA in modulating tumor cell phenotype and
sensitivity to ADT. Our hypothesis is that the expression of this LncRNA promotes tumor progression and
ADT resistance and its expression is modulated by the miRNA cluster. To test our hypothesis two aims
are proposed. In aim 1, we will study the effect of manipulation of the miRNA cluster on transcription of
lncRNA and the stability of the lncRNA transcript using cell culture models. Additionally, we will evaluate the
reciprocal expression pattern of these two classes of ncRNAs in a collection of annotated prostate tumor
tissues using qRT-PCR. Expression profiles of the miRNA cluster and the lncRNA will be correlated with the
disease outcome and risk of biochemical failure. In aim 2, we will determine the function of the lncRNA in
tumor cell growth and behavior, and cellular response to therapeutic agents including ADT and AR
antagonists. This approach is innovative because it investigates the function of a novel lncRNA and its
interaction with miRNAs, and the implication of this crosstalk in progression of aggressive disease and
drug sensitivity of androgen dependent and -independent prostate cancer cells. This study will have a
translational impact on management of prostate cancer as the expression levels will be tested in clinical
samples and establish the premise of a new drug target.

## Key facts

- **NIH application ID:** 9880422
- **Project number:** 5R21CA226611-02
- **Recipient organization:** UNIVERSITY OF CENTRAL FLORIDA
- **Principal Investigator:** RATNA CHAKRABARTI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,296
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880422

## Citation

> US National Institutes of Health, RePORTER application 9880422, Implication of a novel long noncoding RNA in therapy resistant prostate cancer with altered AR signaling (5R21CA226611-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880422. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*