The lncRNA BORG facilitates the survival and chemoresistance of triple-negative breast cancers
| Autor: | Alex J. Gooding, Saba Valadkhan, William P Schiemann, Lalith Gunawardane, Abigail Beard, Bing Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Triple Negative Breast Neoplasms Biology Article 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Line Tumor Replication Protein A Genetics medicine Humans Cytotoxic T cell Doxorubicin Neoplasm Metastasis Cytotoxicity Molecular Biology Cell Proliferation Regulation of gene expression Effector NF-kappa B medicine.disease In vitro Gene Expression Regulation Neoplastic 030104 developmental biology Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Cancer research RNA Long Noncoding human activities Signal Transduction medicine.drug |
| Zdroj: | Oncogene. 38:2020-2041 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Disseminated breast cancer cells employ adaptive molecular responses following cytotoxic therapeutic insult which promotes their survival and subsequent outgrowth. Here we demonstrate that expression of the pro-metastatic lncRNA BORG (BMP/OP-Responsive Gene) is greatly induced within triple-negative breast cancer (TNBC) cells subjected to environmental and chemotherapeutic stresses commonly faced by TNBC cells throughout the metastatic cascade. This stress-mediated induction of BORG expression fosters the survival of TNBC cells and renders them resistant to the cytotoxic effects of doxorubicin both in vitro and in vivo. The chemoresistant traits of BORG depend upon its robust activation of the NF-κB signaling axis via a novel BORG-mediated feed-forward signaling loop, and via its ability to bind and activate RPA1. Indeed, genetic and pharmacologic inhibition of NF-κB signaling or the DNA-binding activity of RPA1 abrogates the pro-survival features of BORG and renders BORG-expressing TNBCs sensitive to doxorubicin-induced cytotoxicity. These findings suggest that therapeutic targeting of BORG or its downstream molecular effectors may provide a novel means to alleviate TNBC recurrence. |
| Databáze: | OpenAIRE |
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