# Role of the lncRNA BORG in Breast Cancer Metastatic Progression and Recurrence

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $454,781

## Abstract

Although metastasis is the most lethal characteristic of breast cancer (BC), our understanding of the
molecular mechanisms that govern this event remains incomplete. Interestingly, many BCs disseminate long
before their primary tumors become symptomatic. In fact, ~50% of women diagnosed with small tumors of the
breast (4 mm) already harbor disseminated carcinoma cells in their bone marrow. Moreover, these
micrometastases escape clinical detection by remaining latent for years before reemerging as incurable
secondary tumors that are insensitive to chemotherapies that were originally effective against the primary tumor.
A major barrier to eradicating BC reflects the paucity of knowledge related to how mammary tumors acquire
metastatic and recurrent phenotypes, which underlies the inability of science and medicine to detect and treat
latent micrometastases. These knowledge deficits are especially problematic for triple-negative breast cancers
(TNBCs), which are highly aggressive and prone to rapid relapse; they also lack FDA-approved targeted
therapies necessary to improve their dismal overall survival rates. Long noncoding RNAs (lncRNAs) have
recently emerged as powerful global regulators of chromatin remodeling and gene expression in diverse
physiological settings, including cell and tissue homeostasis, embryogenesis and development. Moreover, an
ever expanding array of scientific evidence related to the pathophysiology of lncRNAs in human disease led us
to postulate that developing and progressing TNBCs hijack the global chromatin reprogramming ability of
lncRNAs, thereby eliciting emergence from metastatic latency and initiating lethal disease recurrence.
Accordingly, we identified BORG (BMP/OP-Responsive Gene (BORG), as a powerful oncogenic lncRNA whose
aberrant expression correlated with the acquisition of EMT (epithelial-mesenchymal transition) and metastatic
phenotypes in (a) human and murine TNBCs cells; (b) human breast tumors and their corresponding CNS
metastases; and (c) patient-derived xenograft (PDX) models of human BC as compared to normal breast
epithelial cells. Additionally, BORG is sufficient in driving latent disseminated TNBCs cells to reactivate
proliferative programs both in vitro and in vivo, events associated with epigenomic reprogramming operant in
repressing cellular senescence programs, and in activating cell survival programs. Based on these and other
preliminary findings, we hypothesize that BORG drives TNBC metastasis and recurrence by (i) remodeling the
epigenome to reactivate proliferative programs that circumvent quiescence- and senescence-associated
transcriptomes, and (ii) promoting the induction of survival signaling systems coupled to the acquisition of
chemoresistant phenotypes. These hypotheses will be addressed by two Specific Aims. Aim 1 will determine
the mechanisms whereby BORG:TRIM28 complexes form and drive TNBC metastasis and recurrence. We will
identify the minimal BORG determinants necessary to bind ...

## Key facts

- **NIH application ID:** 9832675
- **Project number:** 5R01CA236273-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** William Schiemann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,781
- **Award type:** 5
- **Project period:** 2018-12-06 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832675

## Citation

> US National Institutes of Health, RePORTER application 9832675, Role of the lncRNA BORG in Breast Cancer Metastatic Progression and Recurrence (5R01CA236273-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832675. Licensed CC0.

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