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

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• 作者：Aldema Sas-Chen ; Miriam R Aure ; Limor Leibovich ; Silvia Carvalho ; Yehoshua Enuka ; Cindy Kö ; rner ; Maria Polycarpou-Schwarz ; Sara Lavi ; Nava Nevo ; Yuri Kuznetsov ; Justin Yuan ; Francisco Azuaje ; Oslo Breast Cancer Research Consortium (OSBREAC) ; Igor Ulitsky ; Sven Diederichs ; Stefan Wiemann ; Zohar Yakhini ; Vessela N Kristensen ; Anne-Lise Bø ; rresen-Dale and Yosef Yarden
• 刊名：EMBO Molecular Medicine
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：8
• 期：9
• 页码：1052-1064
• 全文大小：1557K
• ISSN：1757-4684

文摘

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.