Abstract
Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Breast Neoplasms / blood
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Breast Neoplasms / genetics*
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Breast Neoplasms / pathology
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Carboxypeptidases / genetics
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Cell Proliferation / genetics
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Cell-Free Nucleic Acids / blood
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Cell-Free Nucleic Acids / genetics*
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Connexins / genetics
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Disease Progression
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Female
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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MCF-7 Cells
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MicroRNAs / classification
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MicroRNAs / genetics*
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Neoplasm Metastasis
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Neoplasm Proteins / genetics
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RNA, Small Untranslated / blood
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RNA, Small Untranslated / genetics*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Cell-Free Nucleic Acids
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Connexins
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MicroRNAs
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NUPR1 protein, human
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Neoplasm Proteins
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PANX2 protein, human
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RNA, Small Untranslated
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Carboxypeptidases
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SCPEP1 protein, human