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

Journal of Cancer Metastasis and Treatment 2019年第5期4卷 48-61页

作者： Alex J.Gooding kimberly a.parker Saba Valadkhan William P.Schiemann Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA Department of Molecular Biology and Microbiology Case Western Reserve UniversityClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA

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.

关键词： BORG chemoresistance disease recurrence dormancy long noncoding RNA metastasis triple-negative breast cancer

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