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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Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1): A molecular predictor of poor survival in glioblastoma multiforme in Egyptian patients
TL;DR: It is postulated that MALAT1 might have a tumor-suppressive function in GBM in Egyptian population and this specific type of lncRNAs may be included in the lists of both potential prognostic biomarkers and the future therapeutic targets for glioblastomas.
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LCAL1 enhances lung cancer survival via inhibiting AMPK-related antitumor functions
Jun-Yu Li,Zhi-Qiang Luo +1 more
TL;DR: This study provided the first evidence that LCAL1 may support lung cancer survival via inhibiting the activity of AMP-activated protein kinase (AMPK), and revealed that overexpressed LCAL 1 may induce aerobic glycolysis in lung cancer cells through AMPK/HIF1α axis, enhance protein synthesis throughAMPK/mTOR/S6K axis, and suppress autophagic cell death through AM PK/ULK1 pathway.
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Long Noncoding RNA LINC00460 Promotes Cell Progression by Sponging miR-4443 in Head and Neck Squamous Cell Carcinoma.
Meng Li,Xiaomin Zhang,Xu Ding,Yang Zheng,Hongming Du,Huai-Qi Li,Huan Ji,Zeyu Wang,Pengfei Jiao,Xiaomeng Song,Yi Zhong,Heming Wu +11 more
TL;DR: It is shown that LINC00460 was highly expressed in HNSCC tissues and cell lines and could potentially promote cell progression and epithelial mesenchymal transition by sponging miR-4443 in H NSCC.
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Long non-coding RNA DLEU1 exerts an oncogenic function in non-small cell lung cancer.
TL;DR: DLEU1 promoted tumorigenesis and progression of NSCLC, and might be a promising therapeutic target forNSCLC.
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LINC00857 knockdown inhibits cell proliferation and induces apoptosis via involving STAT3 and MET oncogenic proteins in esophageal adenocarcinoma.
Wenmei Su,Lihui Wang,Feiyu Niu,Lei Zou,Chunfang Guo,Zhuwen Wang,Xiao Yang,Jiancong Wu,Yi Lu,Jian Zhang,David G. Beer,Zhixiong Yang,Guoan Chen +12 more
TL;DR: This study finds that the cell proliferation, colony formation, invasion and migration were decreased after LINC00857 knockdown in EAC cell lines, and suggests that Linc00857 may play an important oncogenic role in Eac via STAT3 and MET signaling.
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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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Miao-Chih Tsai,Ohad Manor,Yue Wan,Nima Mosammaparast,Jordon K. Wang,Fei Lan,Yang Shi,Eran Segal,Howard Y. Chang +8 more
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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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