# Identification of functional non-coding RNAs in Human Breast Cancer

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $65,310

## Abstract

Project Summary/Abstract
Aggressive receptor triple-negative breast cancers (TNBCs) lack effective biomarkers or targeted treatments,
posing a major clinical challenge. Examination of primary clinical data from the multi-institutional ISPY trial
found that elevated MYC oncogene expression is a strong indicator of lethal TNBC. A growing body of work
suggests that non-coding RNAs may play an essential role in MYC dependent pathologies, however which of
these may be essential for survival and progress of MYC-driven tumors remains unknown. This proposal will
address the discovery of mechanisms that determine the initiation, risk, and susceptibility for the most deadly
type of breast cancer, basal-like or triple negative breast cancer (TNBC) and the identification of new
mediators of lethality that could lead to tumor regression when blocked. We will test the hypothesis that
MYC-dependent microRNAs ​in vivo and circular RNAs are required for breast tumor formation, maintenance
and recurrence. In an ​unbiased ​in vitro screen of ​~1000 individual locked nucleic acid (LNA) microRNA
antagonists (antimiRs) we identified 13 miRNAs that are required for MYC-dependent cancer progression ​in
human mammary epithelial cells (HMEC) and are highly expressed in “high Myc” breast cancers from the
TCGA dataset​. We found that putative oncogenic circPVT1 had significantly up-regulated expression in
MYC-high TNBC cell line HCC1143 relative to MYC-low T47D breast cancer cells. Thus, we will sequence and
functionally validate Myc dependent miRNAs and circRNAs in these studies. The long-term goal is to identify
critical non-coding RNA targets whose inhibition can block TNBC tumor growth. ​Aim 1: ​Target​ ​MYC-driven​​
​miRNA vulnerabilities​ ​​in​ ​vivo​​: ​We will test the ​in vivo ​efficacy of antimiRs conjugated to folate via RNA
nanoparticles targeting ​miR-16, miR-23, miR-107 and miR-144 using a conditional MYC-driven transgenic
model of breast cancer. Aim 2: ​​​Show ​​circRNAs are​ ​required​ ​for​ ​MYC​ ​driven​ ​breast cancer: ​We plan to
determine the functional consequences of perturbing Myc-dependent circRNAs in human and mouse breast
cancer using lenti-shRNA and circRNA overexpression in ​a high throughput screen. ​My goal is to become a
principal investigator pursuing an independent research program focused on deciphering the disease
mechanisms of breast cancer. ​UCSF is an ideal environment to pursue an interdisciplinary approach to breast
cancer research. Completion of the work proposed will allow me to develop skills and a collaborative network
necessary to compete for tenure track principal investigator positions. This proposal will address the discovery
of non-coding RNA mechanisms that determine the initiation, risk, and susceptibility for the most deadly type of
breast cancer, basal-like or triple negative breast cancer (TNBC) and the identification of new drivers that could
lead to tumor regression when blocked.

## Key facts

- **NIH application ID:** 9841722
- **Project number:** 5F32CA236411-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Matthew Robert Gruner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-12-03 → 2021-12-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841722

## Citation

> US National Institutes of Health, RePORTER application 9841722, Identification of functional non-coding RNAs in Human Breast Cancer (5F32CA236411-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841722. Licensed CC0.

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