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Open AccessJournal ArticleDOI

The Noncoding RNA MALAT1 Is a Critical Regulator of the Metastasis Phenotype of Lung Cancer Cells

TLDR
A loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis with this ncRNA serving as both predictive marker and therapeutic target.
Abstract
The long non-coding RNA MALAT1, also known as MALAT-1 or NEAT2, is a highly conserved nuclear ncRNA and a predictive marker for metastasis development in lung cancer. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements using Zinc Finger Nucleases. The achieved 1000-fold MALAT1 silencing provides a unique loss-of-function model. Proposed mechanisms of action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft. Antisense oligonucleotides blocking MALAT1 prevent metastasis formation after tumor implantation. Thus, targeting MALAT1 with antisense oligonucleotides provides a potential therapeutic approach to prevent lung cancer metastasis with MALAT1 serving as both, predictive marker and therapeutic target. Lastly, regulating gene expression, but not alternative splicing is the critical function of MALAT1 in lung cancer metastasis. In summary, ten years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis.

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Journal ArticleDOI

New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis

TL;DR: This review reflects on different experimental strategies used to study MALAT1’s functions, and discusses the current mechanistic models of this highly abundant and conserved lncRNA.
Journal ArticleDOI

Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer

TL;DR: Systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.
Journal ArticleDOI

Long Noncoding RNAs as Novel Biomarkers Have a Promising Future in Cancer Diagnostics

TL;DR: This review summarizes the detection methods and possible sources of circulating lncRNAs and outlines the biological functions and expression level of the most significant lnc RNAs in tissues, cell lines, and body fluids of different kinds of tumors.
Journal ArticleDOI

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

TL;DR: The existing body of knowledge regarding the key functions of ceRNETs and the emerging roles of some recently discovered ceR NETs in several hallmarks of BC are discussed and the “ceRnome” is proposed for the first time in the present article for RNA research.
Journal ArticleDOI

Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2

TL;DR: It is suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2, and can regulate the expression of LIMk2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH 2), and then promoted cell growth
References
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Journal ArticleDOI

The hallmarks of cancer.

TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

TL;DR: It is shown that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression, indicating that l incRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
Journal ArticleDOI

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Piero Carninci, +197 more
- 02 Sep 2005 - 
TL;DR: Detailed polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes

TL;DR: The results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription

TL;DR: Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes and support a highly interleaved organization of the human transcriptome.
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