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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Aberrant Expression of Pseudogene-Derived lncRNAs as an Alternative Mechanism of Cancer Gene Regulation in Lung Adenocarcinoma.
Greg L. Stewart,K. Enfield,K. Enfield,Adam P. Sage,Victor D. Martinez,Brenda C. Minatel,Michelle E Pewarchuk,Erin A. Marshall,Wan L. Lam +8 more
TL;DR: Evidence is uncovered to suggest the lncRNA-pseudogene-protein-coding gene axis as a prominent mechanism of cancer gene regulation in lung adenocarcinoma, and highlights the clinical utility of exploring the non-Coding regions of the cancer transcriptome.
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LncRNA-MALAT1 as a novel biomarker of cadmium toxicity regulates cell proliferation and apoptosis.
TL;DR: It is suggested that the expression of MALAT1 is upregulated and regulates the cell cycle progression, proliferation, apoptosis, migration and invasion in Cd toxicity.
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Identification of a long non-coding RNA NR_026689 associated with lung carcinogenesis induced by NNK
TL;DR: Using NNK-induced rat lung cancer model and quantitative reverse-transcription PCR, a novel lncRNA was identified, NR_026689, which showed increased expression in lung cancer tissues induced by NNK and the alteration of lncRNAs was specifically observed in lung tissue.
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Decreased long non-coding RNA MTM contributes to gastric cancer cell migration and invasion via modulating MT1F.
TL;DR: Normal decreased expression of MTM was observed in human GC, which might contribute to gastric carcinogenesis by modulating MT1F expression, and a positive correlation between the expression level of M TM andMT1F both in cell and tissue samples is found.
Journal ArticleDOI
Long Non-coding RNA MALAT1 Upregulates ZEB2 Expression to Promote Malignant Progression of Glioma by Attenuating miR-124.
Hongyu Cheng,Haikang Zhao,Xin Xiao,Qian Huang,Wen Zeng,Bo Tian,Tao Ma,Dan Lu,Yulong Jin,Yuqian Li +9 more
TL;DR: A novel pathway of MALAT1/miR-124/ZEB2 that regulates the progression of glioma and might provide a promising strategy forglioma therapy is depicted.
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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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