Does Long Non-coding RNA Increase Late-stage Relapse Risk for HR+ Breast Cancer?

The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

ESR1-bound long non-coding RNAs (lncRNAs) might contribute to late-stage relapse in hormone receptor–positive (HR+) breast cancer, according to research presented at the 2017 San Antonio Breast Cancer Symposium.¹

The finding could lead to breakthroughs in understanding regulatory pathways in late-stage relapse, reported lead study author Christopher Maher, PhD, of the Washington University School of Medicine in St Louis, Missouri, and coauthors.¹

Despite the known benefits of adjuvant endocrine therapy among women with HR+ breast cancer, late-stage relapses can occur beyond 5 years from initial endocrine treatment.

The molecular mechanisms responsible for late-stage relapse are, however, poorly understood. Breast cancer research has focused on protein-coding genes rather than lncRNAs, Dr Maher noted. But accumulating evidence from transcriptome sequencing now suggests that lncRNAs might serve as “master epigenetic regulators” in tumors through interactions with regulatory proteins that modulate gene expression, he said. They are emerging as diagnostic and prognostic biomarkers.

Dr Maher and his colleagues hypothesized that lncRNAs interact with ESR1, increasing the risk of late-stage relapse. They performed transcriptome analyses of late-stage relapse tumors from 24 patients and from 72 primary tumors. RNA immunoprecipitation and transcriptome sequencing (RIP-Seq) were then used to identify ESR1-bound transcripts.

The authors discovered 217 lncRNAs that interact with ESR1, of which 50 were upregulated in late-stage breast cancer. They examined the single most upregulated lncRNA in late-stage relapse, a previously unannotated lncRNA they dubbed LASER-1.

“LASER1 is massively upregulated in late-stage tumors and is almost negligible in the early-stage primary tumors; it seems to be upped only in late-stage tumors,” Dr Maher said.

The authors hope to see their findings lead to the development of LASER-1-targeting agents.

Read more of Cancer Therapy Advisor‘s coverage of the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting by visiting the conference page.

Reference

1. Maher, C, Silva-Fisher J, Eteleeb A, et al. Discovery and characterization of an estrogen bound LncRNA in late-Stage breast cancer. Oral presentation at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX.