# Sequence-specific Hybridization Capture for Discovery  of Proteoform–lncRNA Interactions in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $388,635

## Abstract

Project Summary/Abstract
Long noncoding RNAs (lncRNAs) are vital components of gene expression programs controlling cellular
differentiation and function. lncRNAs act as scaffolds to recruit or sequester effector proteins. They may act in
cis and trans at multiple genomic sites. lncRNAs modulate transcription, chromatin organization, RNA
processing, and translation, and many questions remain unanswered regarding how they influence gene
expression. Recent reviews have detailed several lncRNAs that play key roles in prostate cancer including
regulation of processes in cancer cells such as proliferative signaling, replicative immortality, invasion and
metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. While much
remains to be learned regarding the mechanisms of action involved in lncRNA function, it is abundantly clear
that lncRNAs act in concert with associated proteins to carry out their roles.
Distinguishing between aggressive and indolent prostate cancer is a major conundrum in cancer. In roughly
one-third of the 140,000 intermediate grade cancers (Gleason 7) diagnosed annually, the disease follows a
more aggressive course developing rapid progression of prostate specific antigen (PSA) after treatment and
earlier metastasis and death. During the prior three-year grant period, we discovered several dozen lncRNAs
that distinguish aggressive and indolent prostate cancers, of which four were validated using RT-qPCR. We
also developed the HyPR-MS strategy to permit elucidation of specific RNA-protein interactomes.
In this renewal proposal we seek to further develop and apply a suite of powerful new proteomics tools to study
these and other prostate cancer-relevant lncRNAs and the proteins that associate with them, and use this
capability to reveal important proteomic signatures to distinguish aggressive versus indolent prostate cancer.
These studies will provide a novel and unprecedented view into the nature of the proteoform–lncRNA
interactions that underlie lncRNA function. The delineation of differentially expressed lncRNAs and their
associated proteins/proteoforms will provide insight into the biological mechanisms underlying disease
progression and provide novel therapeutic targets for further development.

## Key facts

- **NIH application ID:** 10307993
- **Project number:** 5R01CA193481-06
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** DAVID F. JARRARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,635
- **Award type:** 5
- **Project period:** 2015-03-04 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307993

## Citation

> US National Institutes of Health, RePORTER application 10307993, Sequence-specific Hybridization Capture for Discovery  of Proteoform–lncRNA Interactions in Prostate Cancer (5R01CA193481-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10307993. Licensed CC0.

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