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EMBO Mol Med. 2016 Sep 1;8(9):1052-64. doi: 10.15252/emmm.201606198. Print 2016 Sep.

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

Author information

1
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
2
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
3
Department of Computer Sciences, Technion-Israel Institute of Technology, Haifa, Israel.
4
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
5
Division of RNA Biology & Cancer (B150), German Cancer Research Center (DKFZ), Heidelberg, Germany Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
6
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
7
Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg.
8
Division of RNA Biology & Cancer (B150), German Cancer Research Center (DKFZ), Heidelberg, Germany Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany German Cancer Consortium (DKTK), Freiburg, Germany Division of Cancer Research, Department of Thoracic Surgery, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany‡
9
Department of Computer Sciences, Technion-Israel Institute of Technology, Haifa, Israel Agilent Laboratories, Petach-Tikva, Israel.
10
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel yosef.yarden@weizmann.ac.il.

Abstract

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.

KEYWORDS:

biomarkers; breast cancer; long noncoding RNA; migration; receptor tyrosine kinase

PMID:
27485121
PMCID:
PMC5009810
DOI:
10.15252/emmm.201606198
[Indexed for MEDLINE]
Free PMC Article

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