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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Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study.
Monika A. Jakubowska,Martyna Sniegocka,Ewa Podgórska,Dominika Michalczyk-Wetula,Krystyna Urbanska,Anna Susz,Leszek Fiedor,Janusz Pyka,Przemyslaw M. Plonka +8 more
TL;DR: The A549-derived tumors growing subcutaneously in nude mice can metastasize and grow on site in the pulmonary tissue, and can represent an alternative for the model of induced metastatic nodule formation, following intravenous administration of the cancerous cells.
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Non-coding Natural Antisense Transcripts: Analysis and Application.
Julian C. Krappinger,Lilli Bonstingl,Katrin Pansy,Katja Sallinger,Nick I. Wreglesworth,Lukas Grinninger,Alexander Deutsch,Amin El-Heliebi,Thomas Kroneis,Ramsay J. McFarlane,Christoph Wilhelm Sensen,Julia Feichtinger +11 more
TL;DR: Non-coding natural antisense transcripts (ncNATs) as discussed by the authors are regulatory RNA sequences that are transcribed in the opposite direction to protein coding genes, pointing out substantial gaps in the analysis and characterisation of these regulatory transcripts.
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Polymorphism in lncRNA AC008392.1 and its interaction with smoking on the risk of lung cancer in a Chinese population.
Xiaoting Lv,Zhigang Cui,Hang Li,Juan Li,Zitai Yang,Yanhong Bi,Min Gao,Baosen Zhou,Zhihua Yin +8 more
TL;DR: It is suggested that lncRNA AC008392.1 rs7248320 may be involved in genetic susceptibility to NSCLC in a Chinese population.
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Copy number amplification and SP1-activated lncRNA MELTF-AS1 regulates tumorigenesis by driving phase separation of YBX1 to activate ANXA8 in non-small cell lung cancer
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Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.
TL;DR: The role of lncRNAs is organized according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.
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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.
Journal ArticleDOI
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Miao-Chih Tsai,Ohad Manor,Yue Wan,Nima Mosammaparast,Jordon K. Wang,Fei Lan,Yang Shi,Eran Segal,Howard Y. Chang +8 more
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
Philipp Kapranov,Jill Cheng,Sujit Dike,David A. Nix,Radharani Duttagupta,Aarron T. Willingham,Peter F. Stadler,Jana Hertel,Jörg Hackermüller,Ivo L. Hofacker,Ian Bell,Evelyn Cheung,Jorg Drenkow,Erica Dumais,Sandeep Patel,Gregg Helt,Madhavan Ganesh,Srinka Ghosh,Antonio Piccolboni,Victor Sementchenko,Hari Tammana,Thomas R. Gingeras +21 more
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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