Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase.
paper
Cited
Public
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- Authors
- Faghihi, Mohammad Ali; Modarresi, Farzaneh; Khalil, Ahmad M; Wood, Douglas E; Sahagan, Barbara G; Morgan, Todd E; Finch, Caleb E; St Laurent, Georges; Kenny, Paul J; Wahlestedt, Claes
- Year
- 2008
- Journal
- Nature medicine
- PMID
- 18587408
- DOI
- 10.1038/nm1784
- PMCID
- PMC2826895
Recent efforts have revealed that numerous protein-coding messenger RNAs have natural antisense transcript partners, most of which seem to be noncoding RNAs. Here we identify a conserved noncoding antisense transcript for beta-secretase-1 (BACE1), a crucial enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript (BACE1-AS) regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. Upon exposure to various cell stressors including amyloid-beta 1-42 (Abeta 1-42), expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Abeta 1-42 through a post-transcriptional feed-forward mechanism. BACE1-AS concentrations were elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. These data show that BACE1 mRNA expression is under the control of a regulatory noncoding RNA that may drive Alzheimer's disease-associated pathophysiology. In summary, we report that a long noncoding RNA is directly implicated in the increased abundance of Abeta 1-42 in Alzheimer's disease.
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| HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion. | Ros G et al. | β | 2019 | β |
| HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3. | Li B et al. | β | 2019 | β |
| HuR interacts with lincBRN1a and lincBRN1b during neuronal stem cells differentiation. | Carelli S et al. | β | 2019 | β |
| <i>Beta-Secretase</i> 1 (<i>BACE1</i>) Is Down-Regulated in Invasive Ductal Carcinoma of Breast. | Yaghoobi H et al. | β | 2019 | β |
| Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer's disease. | Cao M et al. | β | 2019 | β |
| Identification of Key Long Non-Coding RNAs in the Pathology of Alzheimer's Disease and their Functions Based on Genome-Wide Associations Study, Microarray, and RNA-seq Data. | Han Z et al. | β | 2019 | β |
| Identification of the Potential Key Long Non-coding RNAs in Aged Mice With Postoperative Cognitive Dysfunction. | Li M et al. | β | 2019 | β |
| <i>ESR1</i>-Stabilizing Long Noncoding RNA <i>TMPO-AS1</i> Promotes Hormone-Refractory Breast Cancer Progression. | Mitobe Y et al. | β | 2019 | β |
| Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer. | Zhu L et al. | β | 2019 | β |
| Integrated identification of key genes and pathways in Alzheimer's disease via comprehensive bioinformatical analyses. | Yan T et al. | β | 2019 | β |
| Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response. | Huang J et al. | β | 2019 | β |
| Invited Review: Long non-coding RNAs: important regulators in the development, function and disorders of the central nervous system. | Cuevas-Diaz Duran R et al. | β | 2019 | β |
| <i>SATB2-AS1</i> Suppresses Colorectal Carcinoma Aggressiveness by Inhibiting SATB2-Dependent <i>Snail</i> Transcription and Epithelial-Mesenchymal Transition. | Wang YQ et al. | β | 2019 | β |
| Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer. | Liu P et al. | β | 2019 | β |
| LncRNA17A regulates autophagy and apoptosis of SH-SY5Y cell line as an in vitro model for Alzheimer's disease. | Wang X et al. | β | 2019 | β |
| LncRNA2Target v2.0: a comprehensive database for target genes of lncRNAs in human and mouse. | Cheng L et al. | β | 2019 | β |
| LncRNA HOTAIR-mediated Wnt/Ξ²-catenin network modeling to predict and validate therapeutic targets for cartilage damage. | Zhou W et al. | β | 2019 | β |
| Long Non-coding RNA BACE1-AS May Serve as an Alzheimer's Disease Blood-Based Biomarker. | Fotuhi SN et al. | β | 2019 | β |
| Long Noncoding RNA Can Be a Probable Mechanism and a Novel Target for Diagnosis and Therapy in Fragile X Syndrome. | Huang G et al. | β | 2019 | β |
| Long noncoding RNA CASC11 promotes osteosarcoma metastasis by suppressing degradation of snail mRNA. | Song K et al. | β | 2019 | β |
| Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21. | Lyu K et al. | β | 2019 | β |
| Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation. | Zhang H et al. | β | 2019 | β |
| Long noncoding RNA NORAD regulates MPP+-induced Parkinson's disease model cells. | Song Q et al. | β | 2019 | β |
| Long noncoding RNA PXN-AS1-L promotes the malignancy of nasopharyngeal carcinoma cells via upregulation of SAPCD2. | Jia X et al. | β | 2019 | β |
| Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson's Disease Patients. | Elkouris M et al. | β | 2019 | β |
| Long Noncoding RNAs: Emerging Players in Medulloblastoma. | Laneve P et al. | β | 2019 | β |
| Long Noncoding RNAs in Development and Regeneration of the Neural Lineage. | Hezroni H et al. | β | 2019 | β |
| Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease. | Fernandes JCR et al. | β | 2019 | β |
| Long noncoding RNAs: Novel regulators of virus-host interactions. | Liu S et al. | β | 2019 | β |
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| Mechanisms of Antisense Transcription Initiation with Implications in Gene Expression, Genomic Integrity and Disease Pathogenesis. | Barman P et al. | β | 2019 | β |
| miR-124-3p availability is antagonized by LncRNA-MALAT1 for Slug-induced tumor metastasis in hepatocellular carcinoma. | Cui RJ et al. | β | 2019 | β |
| Multimodal Long Noncoding RNA Interaction Networks: Control Panels for Cell Fate Specification. | Smith KN et al. | β | 2019 | β |
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| Non-Coding RNA Networks in ALK-Positive Anaplastic-Large Cell Lymphoma. | Fuchs S et al. | β | 2019 | β |
| Noncoding RNAs in acute kidney injury. | Ren GL et al. | β | 2019 | β |
| Noncoding RNAs in the Vascular System Response to Oxidative Stress. | Fuschi P et al. | β | 2019 | β |
| NRF2/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer's models. | Bahn G et al. | β | 2019 | β |
| Nutrient Stress-Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression. | Deng SJ et al. | β | 2019 | β |
| Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play A Role? | Cirillo F et al. | β | 2019 | β |
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| PTB-AS, a Novel Natural Antisense Transcript, Promotes Glioma Progression by Improving PTBP1 mRNA Stability with SND1. | Zhu L et al. | β | 2019 | β |
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| RPITER: A Hierarchical Deep Learning Framework for ncRNAβ»Protein Interaction Prediction. | Peng C et al. | β | 2019 | β |
| Silencing of Long Noncoding RNA SOX21-AS1 Relieves Neuronal Oxidative Stress Injury in Mice with Alzheimer's Disease by Upregulating FZD3/5 via the Wnt Signaling Pathway. | Zhang L et al. | β | 2019 | β |
| Sirt1 antisense transcript is down-regulated in human tumors. | Mokhberian N et al. | β | 2019 | β |
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| The Emerging Role of Major Regulatory RNAs in Cancer Control. | Dai X et al. | β | 2019 | β |
| The importance of long non-coding RNAs in neuropsychiatric disorders. | Hosseini E et al. | β | 2019 | β |
| The lncRNA, Nespas, Is Associated with Osteoarthritis Progression and Serves as a Potential New Prognostic Biomarker. | Park S et al. | β | 2019 | β |
| The long-non-coding RNA NEAT1 is a novel target for Alzheimer's disease progression via miR-124/BACE1 axis. | Zhao MY et al. | β | 2019 | β |
| The long noncoding RNA uc.294 is upregulated in early-onset pre-eclampsia and inhibits proliferation, invasion of trophoblast cells (HTR-8/SVneo). | Song X et al. | β | 2019 | β |
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| Ξ²-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer. | Esfandi F et al. | β | 2019 | β |
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| A modified immunofluorescence <i>in situ</i> hybridization method to detect long non-coding RNAs and proteins in frozen spinal cord sections. | Meng C et al. | β | 2018 | β |
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| Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease. | Yu B et al. | β | 2018 | β |
| A Novel Probability Model for LncRNAβ»Disease Association Prediction Based on the NaΓ―ve Bayesian Classifier. | Yu J et al. | β | 2018 | β |
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| BACE1 elevation engendered by GGA3 deletion increases Ξ²-amyloid pathology in association with APP elevation and decreased CHL1 processing in 5XFAD mice. | Kim W et al. | β | 2018 | β |
| BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease. | Bao J et al. | β | 2018 | β |
| Competing Endogenous RNA Regulations in Neurodegenerative Disorders: Current Challenges and Emerging Insights. | Cai Y et al. | β | 2018 | β |
| Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling. | Zhang Y et al. | β | 2018 | β |
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| Crosstalk mechanisms between the WNT signaling pathway and long non-coding RNAs. | Zarkou V et al. | β | 2018 | β |
| Cytoplasmic functions of long noncoding RNAs. | Noh JH et al. | β | 2018 | β |
| Deficiency in the nuclear long noncoding RNA <i>Charme</i> causes myogenic defects and heart remodeling in mice. | Ballarino M et al. | β | 2018 | β |
| Developments in lncRNA drug discovery: where are we heading? | Blokhin I et al. | β | 2018 | β |
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| Expression analysis of beta-secretase 1 (BACE1) and its naturally occurring antisense (BACE1-AS) in blood of epileptic patients. | Mazdeh M et al. | β | 2018 | β |
| Expression profile analysis of long non-coding RNAs involved in the metformin-inhibited gluconeogenesis of primary mouse hepatocytes. | Wang Y et al. | β | 2018 | β |
| Forging our understanding of lncRNAs in the brain. | Andersen RE et al. | β | 2018 | β |
| Functional role of lncRNA LOC101927497 in N-methyl-N'-nitro-N-nitrosoguanidine-induced malignantly transformed human gastric epithelial cells. | Luo Y et al. | β | 2018 | β |
| Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour. | Chen Y et al. | β | 2018 | β |
| HIF-2Ξ± activated lncRNA NEAT1 promotes hepatocellular carcinoma cell invasion and metastasis by affecting the epithelial-mesenchymal transition. | Zheng X et al. | β | 2018 | β |
| Identification of functional features of synthetic SINEUPs, antisense lncRNAs that specifically enhance protein translation. | Takahashi H et al. | β | 2018 | β |
| IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p. | Zhou Y et al. | β | 2018 | β |
| Increased levels of the long noncoding RNA, HOXA-AS3, promote proliferation of A549 cells. | Zhang H et al. | β | 2018 | β |
| Inhibition of HDAC3 reverses Alzheimer's disease-related pathologies in vitro and in the 3xTg-AD mouse model. | Janczura KJ et al. | β | 2018 | β |
| Insights into the roles of lncRNAs in skeletal and dental diseases. | Li Y et al. | β | 2018 | β |
| Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer's Disease. | Winick-Ng W et al. | β | 2018 | β |
| Knockdown of BACE1-AS by siRNA improves memory and learning behaviors in Alzheimer's disease animal model. | Zhang W et al. | β | 2018 | β |
| Knockdown of LncRNA MAPT-AS1 inhibites proliferation and migration and sensitizes cancer cells to paclitaxel by regulating MAPT expression in ER-negative breast cancers. | Pan Y et al. | β | 2018 | β |
| Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells. | Ruan W et al. | β | 2018 | β |
| Landscape of long non-coding RNAs in Trichophyton mentagrophytes-induced rabbit dermatophytosis lesional skin and normal skin. | Xiao W et al. | β | 2018 | β |
| Lnc-ISG20 Inhibits Influenza A Virus Replication by Enhancing ISG20 Expression. | Chai W et al. | β | 2018 | β |
| LncmiRSRN: identification and analysis of long non-coding RNA related miRNA sponge regulatory network in human cancer. | Zhang J et al. | β | 2018 | β |
| LncRNA Expression Signature in Prediction of the Prognosis of Lung Adenocarcinoma. | Li L et al. | β | 2018 | β |
| LncRNA IDH1-AS1 links the functions of c-Myc and HIF1Ξ± via IDH1 to regulate the Warburg effect. | Xiang S et al. | β | 2018 | β |
| LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212. | Yu F et al. | β | 2018 | β |
| LncRNA NCK1-AS1 promotes proliferation and induces cell cycle progression by crosstalk NCK1-AS1/miR-6857/CDK1 pathway. | Li H et al. | β | 2018 | β |
| lncRNA profile study reveals the mRNAs and lncRNAs associated with docetaxel resistance in breast cancer cells. | Huang P et al. | β | 2018 | β |
| lncRNAs, DNA Methylation, and the Pathobiology of Exfoliation Glaucoma. | Johnson WM et al. | β | 2018 | β |
| LncRNAs in genetic basis of glaucoma. | CissΓ© Y et al. | β | 2018 | β |
| Long noncoding RNA expression profile and association with SLEDAI score in monocyte-derived dendritic cells from patients with systematic lupus erythematosus. | Wang Y et al. | β | 2018 | β |
| Long Non-coding RNA in Neuronal Development and Neurological Disorders. | Li L et al. | β | 2018 | β |
| Long non-coding RNA <i>RAB11B-AS1</i> prevents osteosarcoma development and progression via its natural antisense transcript <i>RAB11B</i>. | Chen Z et al. | β | 2018 | β |
| Long Non-Coding RNA-Mediated Regulation of the Interferon Response: A New Perspective on a Familiar Theme. | Valadkhan S et al. | β | 2018 | β |
| Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma. | Yuan S et al. | β | 2018 | β |
| Long non-coding RNA p10247, high expressed in breast cancer (lncRNA-BCHE), is correlated with metastasis. | Yang YX et al. | β | 2018 | β |
| Long non-coding RNA reprogramming (lncRNA-ROR) regulates cell apoptosis and autophagy in chondrocytes. | Yang Z et al. | β | 2018 | β |
| Long Noncoding RNAs and Cardiac Disease. | Greco S et al. | β | 2018 | β |
| Long non-coding RNAs: An essential emerging field in kidney pathogenesis. | Moghaddas Sani H et al. | β | 2018 | β |
| Long non-coding RNAs in ischemic stroke. | Bao MH et al. | β | 2018 | β |
| Long Non-Coding RNAs in Multifactorial Diseases: Another Layer of Complexity. | Cipolla GA et al. | β | 2018 | β |
| Long Non-Coding RNAs in Neuronal Aging. | Pereira Fernandes D et al. | β | 2018 | β |
| Long Non-coding RNAs, Novel Culprits, or Bodyguards in Neurodegenerative Diseases. | Wang DQ et al. | β | 2018 | β |
| MALAT1/miR-127-5p Regulates Osteopontin (OPN)-Mediated Proliferation of Human Chondrocytes Through PI3K/Akt Pathway. | Liang J et al. | β | 2018 | β |
| Microarray analysis of an synthetic Ξ±-synuclein induced cellular model reveals the expression profile of long non-coding RNA in Parkinson's disease. | Lin D et al. | β | 2018 | β |
| Microarray expression profiling and co-expression network analysis of circulating LncRNAs and mRNAs associated with neurotoxicity induced by BPA. | Pang W et al. | β | 2018 | β |
| MicroRNAs link chronic inflammation in childhood to growth impairment and insulin-resistance. | Cirillo F et al. | β | 2018 | β |
| Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis. | Hu G et al. | β | 2018 | β |
| Multiple Layers of <i>CDK5R1</i> Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs. | Spreafico M et al. | β | 2018 | β |
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| Noncoding RNAs in disease. | Lekka E et al. | β | 2018 | β |
| Non-Coding Transcriptome Maps across Twenty Tissues of the Korean Black Chicken, Yeonsan Ogye. | Hong H et al. | β | 2018 | β |
| OverGeneDB: a database of 5' end protein coding overlapping genes in human and mouse genomes. | Rosikiewicz W et al. | β | 2018 | β |
| Prediction of lncRNA-disease associations based on inductive matrix completion. | Lu C et al. | β | 2018 | β |
| Profiling long noncoding RNA of multi-tissue transcriptome enhances porcine noncoding genome annotation. | Zhao P et al. | β | 2018 | β |
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| Selective expression of long non-coding RNAs in a breast cancer cell progression model. | Tracy KM et al. | β | 2018 | β |
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| Synaptic Dysfunction in Alzheimer's Disease: AΞ², Tau, and Epigenetic Alterations. | Li K et al. | β | 2018 | β |
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| Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes Glioblastoma. | Li J et al. | β | 2018 | β |
| Targeting the FOXM1-regulated long noncoding RNA TUG1 in osteosarcoma. | Li Y et al. | β | 2018 | β |
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| The Epigenetics of Alzheimer's Disease: Factors and Therapeutic Implications. | Liu X et al. | β | 2018 | β |
| The Ever-Evolving Concept of the Gene: The Use of RNA/Protein Experimental Techniques to Understand Genome Functions. | Cipriano A et al. | β | 2018 | β |
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| The long noncoding RNA landscape in cardiovascular disease: a brief update. | Salamon I et al. | β | 2018 | β |
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| The role of long non-coding RNAs in cardiac development and disease. | GarcΓa-Padilla C et al. | β | 2018 | β |
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| The Role of Long Noncoding RNAs in Diabetic Alzheimer's Disease. | Kim YK et al. | β | 2018 | β |
| The rs13388259 Intergenic Polymorphism in the Genomic Context of the <i>BCYRN1</i> Gene Is Associated with Parkinson's Disease in the Hungarian Population. | MΓ‘rki S et al. | β | 2018 | β |
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| Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease. | Powell SK et al. | β | 2017 | β |
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| Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity. | Li W et al. | β | 2017 | β |
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