Journal
BREAST
Volume 46, Issue -, Pages 64-69Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.breast.2019.05.003
Keywords
Extracellular vesicle; Exosome; Long non-coding RNA; HOTAIR; Breast cancer; HER2/ErbB2
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Funding
- National Health Research Institutes [NHRI-EX106-10602BI]
- Ministry of Science and Technology [MOST-106-2320-B-039-046]
- Ministry of Health and Welfare [MOHW107-TDU-B-212-112015]
- China Medical University Hospital [DMR-CELL-17025]
- Drug Development Center, China Medical University from The Featured Areas Research Center Program
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Cancer cells are known to produce and secret extracellular vesicles for intercellular communication through the carried cargos. HOTAIR (HOX transcript antisense intergenic RNA), a well-studied long non-coding RNA (IncRNA), plays a critical role in cancer progression. In several cancer types it has been shown that HOTAIR-containing exosomes are produced by cancer cells. Here we show that circulatory exosomal HOTAIR is present in breast cancer patients and explores the pathological correlation with the disease. Exosomes were isolated by matrix-based precipitation from conditioned media of cultured breast cancer cell lines as well as blood samples of recently recruited breast cancer patients. HOTAIR RNA in exosomes was detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Expression of exosomal HOTAIR was positively correlated with status of the receptor tyrosine kinase (RTK) ErbB2 (also known as HER2/neu) in tumor tissues. The causal correlation of ErbB2 and HOTAIR was validated in isogenic breast cancer cell lines with and without ectopic ErbB2 expression. Our finding provides a molecular basis to develop novel liquid biopsy biomarkers and targeted therapies with improved precision for malignant breast cancer. (C) 2019 Elsevier Ltd. All rights reserved.
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