LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis
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Open Access
- 12 June 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 5 (6), e1287
- https://doi.org/10.1038/cddis.2014.249
Abstract
LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.Keywords
This publication has 52 references indexed in Scilit:
- Modulation of hypoxia-signaling pathways by extracellular long non-coding RNA regulator of reprogrammingJournal of Cell Science, 2014
- Endogenous miRNA Sponge lincRNA-RoR Regulates Oct4, Nanog, and Sox2 in Human Embryonic Stem Cell Self-RenewalDevelopmental Cell, 2013
- Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expressionThe FEBS Journal, 2013
- A nucleolar protein, H19 opposite tumor suppressor ( HOTS ), is a tumor growth inhibitor encoded by a human imprinted H19 antisense transcriptProceedings of the National Academy of Sciences of the United States of America, 2011
- Molecular Mechanisms of Long Noncoding RNAsMolecular Cell, 2011
- Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNAGenes & Development, 2010
- Epithelial-Mesenchymal Transitions in Development and DiseaseCell, 2009
- Transitions between epithelial and mesenchymal states in development and diseaseSeminars in Cell & Developmental Biology, 2008
- Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?Nature Reviews Cancer, 2007
- Discrimination of Non-Protein-Coding Transcripts from Protein-Coding mRNARNA Biology, 2006