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LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer

Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal‐like subtype associates with increased EGFR signaling, while another, the...

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Autores principales: Sas‐Chen, Aldema, Aure, Miriam R, Leibovich, Limor, Carvalho, Silvia, Enuka, Yehoshua, Körner, Cindy, Polycarpou‐Schwarz, Maria, Lavi, Sara, Nevo, Nava, Kuznetsov, Yuri, Yuan, Justin, Azuaje, Francisco, Ulitsky, Igor, Diederichs, Sven, Wiemann, Stefan, Yakhini, Zohar, Kristensen, Vessela N, Børresen‐Dale, Anne‐Lise, Yarden, Yosef, Sauer, Torill, Geisler, Jürgen, Hofvind, Solveig, Bathen, Tone F, Borgen, Elin, Engebråten, Olav, Fodstad, Øystein, Garred, Øystein, Geitvik, Gry Aarum, Kåresen, Rolf, Naume, Bjørn, Mælandsmo, Gunhild Mari, Russnes, Hege G, Schlichting, Ellen, Sørlie, Therese, Lingjærde, Ole Christian, Sahlberg, Kristine Kleivi, Skjerven, Helle Kristine, Fritzman, Britt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009810/
https://www.ncbi.nlm.nih.gov/pubmed/27485121
http://dx.doi.org/10.15252/emmm.201606198
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author Sas‐Chen, Aldema
Aure, Miriam R
Leibovich, Limor
Carvalho, Silvia
Enuka, Yehoshua
Körner, Cindy
Polycarpou‐Schwarz, Maria
Lavi, Sara
Nevo, Nava
Kuznetsov, Yuri
Yuan, Justin
Azuaje, Francisco
Ulitsky, Igor
Diederichs, Sven
Wiemann, Stefan
Yakhini, Zohar
Kristensen, Vessela N
Børresen‐Dale, Anne‐Lise
Yarden, Yosef
Sauer, Torill
Geisler, Jürgen
Hofvind, Solveig
Bathen, Tone F
Borgen, Elin
Engebråten, Olav
Fodstad, Øystein
Garred, Øystein
Geitvik, Gry Aarum
Kåresen, Rolf
Naume, Bjørn
Mælandsmo, Gunhild Mari
Russnes, Hege G
Schlichting, Ellen
Sørlie, Therese
Lingjærde, Ole Christian
Sahlberg, Kristine Kleivi
Skjerven, Helle Kristine
Fritzman, Britt
author_facet Sas‐Chen, Aldema
Aure, Miriam R
Leibovich, Limor
Carvalho, Silvia
Enuka, Yehoshua
Körner, Cindy
Polycarpou‐Schwarz, Maria
Lavi, Sara
Nevo, Nava
Kuznetsov, Yuri
Yuan, Justin
Azuaje, Francisco
Ulitsky, Igor
Diederichs, Sven
Wiemann, Stefan
Yakhini, Zohar
Kristensen, Vessela N
Børresen‐Dale, Anne‐Lise
Yarden, Yosef
Sauer, Torill
Geisler, Jürgen
Hofvind, Solveig
Bathen, Tone F
Borgen, Elin
Engebråten, Olav
Fodstad, Øystein
Garred, Øystein
Geitvik, Gry Aarum
Kåresen, Rolf
Naume, Bjørn
Mælandsmo, Gunhild Mari
Russnes, Hege G
Schlichting, Ellen
Sørlie, Therese
Lingjærde, Ole Christian
Sahlberg, Kristine Kleivi
Skjerven, Helle Kristine
Fritzman, Britt
author_sort Sas‐Chen, Aldema
collection PubMed
description Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal‐like subtype associates with increased EGFR signaling, while another, the HER2‐enriched subtype, engages a kin of EGFR. Based on the premise that EGFR‐regulated lncRNAs might control the aggressiveness of basal‐like tumors, we identified multiple EGFR‐inducible lncRNAs in basal‐like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal‐like and in HER2‐positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.
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spelling pubmed-50098102016-11-14 LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer Sas‐Chen, Aldema Aure, Miriam R Leibovich, Limor Carvalho, Silvia Enuka, Yehoshua Körner, Cindy Polycarpou‐Schwarz, Maria Lavi, Sara Nevo, Nava Kuznetsov, Yuri Yuan, Justin Azuaje, Francisco Ulitsky, Igor Diederichs, Sven Wiemann, Stefan Yakhini, Zohar Kristensen, Vessela N Børresen‐Dale, Anne‐Lise Yarden, Yosef Sauer, Torill Geisler, Jürgen Hofvind, Solveig Bathen, Tone F Borgen, Elin Engebråten, Olav Fodstad, Øystein Garred, Øystein Geitvik, Gry Aarum Kåresen, Rolf Naume, Bjørn Mælandsmo, Gunhild Mari Russnes, Hege G Schlichting, Ellen Sørlie, Therese Lingjærde, Ole Christian Sahlberg, Kristine Kleivi Skjerven, Helle Kristine Fritzman, Britt EMBO Mol Med Research Articles Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal‐like subtype associates with increased EGFR signaling, while another, the HER2‐enriched subtype, engages a kin of EGFR. Based on the premise that EGFR‐regulated lncRNAs might control the aggressiveness of basal‐like tumors, we identified multiple EGFR‐inducible lncRNAs in basal‐like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal‐like and in HER2‐positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers. John Wiley and Sons Inc. 2016-08-03 2016-09 /pmc/articles/PMC5009810/ /pubmed/27485121 http://dx.doi.org/10.15252/emmm.201606198 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sas‐Chen, Aldema
Aure, Miriam R
Leibovich, Limor
Carvalho, Silvia
Enuka, Yehoshua
Körner, Cindy
Polycarpou‐Schwarz, Maria
Lavi, Sara
Nevo, Nava
Kuznetsov, Yuri
Yuan, Justin
Azuaje, Francisco
Ulitsky, Igor
Diederichs, Sven
Wiemann, Stefan
Yakhini, Zohar
Kristensen, Vessela N
Børresen‐Dale, Anne‐Lise
Yarden, Yosef
Sauer, Torill
Geisler, Jürgen
Hofvind, Solveig
Bathen, Tone F
Borgen, Elin
Engebråten, Olav
Fodstad, Øystein
Garred, Øystein
Geitvik, Gry Aarum
Kåresen, Rolf
Naume, Bjørn
Mælandsmo, Gunhild Mari
Russnes, Hege G
Schlichting, Ellen
Sørlie, Therese
Lingjærde, Ole Christian
Sahlberg, Kristine Kleivi
Skjerven, Helle Kristine
Fritzman, Britt
LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title_full LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title_fullStr LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title_full_unstemmed LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title_short LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer
title_sort limt is a novel metastasis inhibiting lncrna suppressed by egf and downregulated in aggressive breast cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009810/
https://www.ncbi.nlm.nih.gov/pubmed/27485121
http://dx.doi.org/10.15252/emmm.201606198
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