The Noncoding RNA MALAT1 Is a Critical Regulator of the Metastasis Phenotype of Lung Cancer Cells
Tony Gutschner,Monika Hämmerle,Moritz Eißmann,Jeff Hsu,Youngsoo Kim,Gene Hung,Alexey S. Revenko,Gayatri Arun,Marion Stentrup,Matthias Groß,Martin Zörnig,A. Robert MacLeod,David L. Spector,Sven Diederichs +13 more
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.read more
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Noncoding RNAs in breast cancer
TL;DR: The roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis are described and discussed, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor nc RNAs.
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Highly expressed lncRNA CRNDE promotes cell proliferation through Wnt/β-catenin signaling in renal cell carcinoma.
TL;DR: It is found that lncRNA CRNDE is highly expressed in RCC malignant tissues and the heightenedCRNDE robustly promotes RCC cell proliferation through activating Wnt/β-catenin signaling; the findings enlarge the knowledge in the molecular pathology of RCC tumorigenesis.
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A Novel Long Non-Coding RNA, SOX21-AS1, Indicates a Poor Prognosis and Promotes Lung Adenocarcinoma Proliferation.
TL;DR: It is demonstrated that SOX21-AS1 is involved in the development and progression of LUAD and that SOx21-as1 may be a potential diagnostic factor as well as a target for new therapies for patients with LUAD.
Journal ArticleDOI
Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis.
TL;DR: MALAT-1 may serve as a molecular marker for cancer metastasis and prognosis and is associated with lymph node metastasis, distant metastasis (DM), and overall survival (OS) in patients with high MALAT1 expression.
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Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus
Marco Mineo,Shawn M. Lyons,Mykola Zdioruk,Niklas von Spreckelsen,Niklas von Spreckelsen,Ruben Ferrer-Luna,Ruben Ferrer-Luna,Hirotaka Ito,Quazim A. Alayo,Prakash Kharel,Alexandra M Giantini Larsen,William Y. Fan,Sophia Auduong,Korneel Grauwet,Carmela Passaro,Jasneet Kaur Khalsa,Khalid Shah,David A. Reardon,Keith L. Ligon,Keith L. Ligon,Rameen Beroukhim,Rameen Beroukhim,Rameen Beroukhim,Hiroshi Nakashima,Pavel Ivanov,Pavel Ivanov,Paul A. Anderson,Paul A. Anderson,Sean E. Lawler,E. Antonio Chiocca +29 more
TL;DR: A mechanism of tumor IFNγ signaling regulation mediated by the lncRNA INCR1 is introduced and suggest a therapeutic target for cancer immunotherapy.
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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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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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