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
Citations
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Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion.
TL;DR: Increased lncRNA MVIH levels were increased in NSCLC tissues compared with adjacent normal tissues and its expression level was significantly correlated with TNM stages, tumor size, and lymph node metastasis.
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Down-Regulation of LncRNA DGCR5 Correlates with Poor Prognosis in Hepatocellular Carcinoma.
Ruyi Huang,Xiaochen Wang,Wenjie Zhang,Guangyan Zhangyuan,Kangpeng Jin,Weiwei Yu,Yu Xie,Xiaoliang Xu,Hai Wang,Beicheng Sun +9 more
TL;DR: The results suggest that DGCR5 may be a participator in HCC and can serve as potential biomarker for the diagnosis and prognosis in H CC.
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LncRNAs and neoplasia.
Mustafa Isin,Nejat Dalay +1 more
TL;DR: The current knowledge on lncRNAs and their function as mediators of tumor development is summarized and improved understanding of the roles played by lnc RNAs in cancer will lead to more effective therapeutic strategies.
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Long noncoding RNA SNHG16 targets miR-146a-5p/CCL5 to regulate LPS-induced WI-38 cell apoptosis and inflammation in acute pneumonia
TL;DR: SNHG16 regulated LPS-induced inflammation injury in WI-38 cells through competitively binding miR-146a-5p with CCL5 further mediating JNK and NF-κB pathways, which sheds novel light on diagnostics and therapeutics in pneumonia.
Journal ArticleDOI
Immune system-mediated atherosclerosis caused by deficiency of long non-coding RNA MALAT1 in ApoE-/-mice.
Martina Gast,Bernhard H. Rauch,Shinichi Nakagawa,Arash Haghikia,Andrzej Jasina,Jan Haas,Neetika Nath,Neetika Nath,Lars Riff Jensen,Lars Riff Jensen,Andrea Stroux,Andreas Böhm,Julian Friebel,Ursula Rauch,Carsten Skurk,Stefan Blankenberg,Tanja Zeller,Kannanganattu V. Prasanth,Benjamin Meder,Andreas W. Kuss,Andreas W. Kuss,Ulf Landmesser,Wolfgang Poller +22 more
TL;DR: A molecular circuit involving the MALAT1-mascRNA system, interactions between MALat1 and NEAT1, and key immune effector molecules, cumulatively impacting upon the development of atherosclerosis is suggested.
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Journal ArticleDOI
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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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