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Gooding et al. J Cancer Metastasis Treat 2019;5:41 Journal of Cancer
DOI: 10.20517/2394-4722.2019.11 Metastasis and Treatment

Review Open Access

The lncRNA BORG: a novel inducer of TNBC
metastasis, chemoresistance, and disease

recurrence

Alex J. Gooding , Kimberly A. Parker , Saba Valadkhan , William P. Schiemann 4
3
1
2
1 Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
2 Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
3 Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106, USA.
4 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

Correspondence to: Dr. William P. Schiemann, Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein
Research Building, Room 2131, 2103 Cornell Road Cleveland, OH 44106, USA. E-mail: william.schiemann@case.edu; Dr. Saba
Valadkhan, Department of Molecular Biology and Microbiology, Case Western Reserve University, Wood Building, 10900 Euclid
Avenue, Cleveland, OH 44106, USA. E-mail: saba.valadkhan@case.edu
How to cite this article: Gooding AJ, Parker KA, Valadkhan S, Schiemann WP. The lncRNA BORG: a novel inducer of TNBC
metastasis, chemoresistance, and disease recurrence. J Cancer Metastasis Treat 2019;5:41.
http://dx.doi.org/10.20517/2394-4722.2019.11

Received: 24 Jan 2019 First Decision: 1 Apr 2019 Revised: 12 Apr 2019 Accepted: 15 Apr 2019 Published: 10 May 2019

Science Editor: Ren Xu Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Although greater than 90% of breast cancer-related mortality can be attributed to metastases, the molecular
mechanisms underpinning the dissemination of primary breast tumor cells and their ability to establish malignant
lesions in distant tissues remain incompletely understood. Genomic and transcriptomic analyses identified a class
of transcripts called long noncoding RNA (lncRNA), which interact both directly and indirectly with key components
of gene regulatory networks to alter cell proliferation, invasion, and metastasis. We identified a pro-metastatic
lncRNA BMP/OP-Responsive Gene (BORG) whose aberrant expression promotes metastatic relapse by reactivating
proliferative programs in dormant disseminated tumor cells (DTCs). BORG expression is broadly and strongly
induced by environmental and chemotherapeutic stresses, a transcriptional response that facilitates the survival
of DTCs. Transcriptomic reprogramming in response to BORG resulted in robust signaling via survival and viability
pathways, as well as decreased activation of cell death pathways. As such, BORG expression acts as a (1) marker
capable of predicting which breast cancer patients are predisposed to develop secondary metastatic lesions; and
(2) unique therapeutic target to maximize chemosensitivity of DTCs. Here we review the molecular and cellular
factors that contribute to the pathophysiological activities of BORG during its regulation of breast cancer metastasis,
chemoresistance, and disease recurrence.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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