ArticleThe Journal of biological chemistry2010
Chromosome 21-derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 116 citations in OpenAlex.
- Review
- Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment.Cellular & molecular biology letters · 2022Review
- Emerging roles for MEF2 in brain development and mental disorders.Current opinion in neurobiology · 2019Review
- Astrocytic miR-324-5p is essential for synaptic formation by suppressing the secretion of CCL5 from astrocytes.Cell death & disease · 2019Article
- Effect of Postmortem Interval and Years in Storage on RNA Quality of Tissue at a Repository of the NIH NeuroBioBank.Biopreservation and biobanking · 2018Article
- Review
- MicroRNA Expression Profile in the Prenatal Amniotic Fluid Samples of Pregnant Women with Down Syndrome.Balkan medical journal · 2018Article
- Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation.Molecular neurobiology · 2018Review
- Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer.International journal of molecular sciences · 2016Article
- Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology.Molecular autism · 2016Article
- Article
- The epigenetics of aging and neurodegeneration.Progress in neurobiology · 2015Review
- Aneuploidy and chromosomal instability in cancer: a jackpot to chaos.Cell division · 2015Article
- MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity.FEBS open bio · 2015Article
- Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases.Stem cells international · 2015Review
- Rett syndrome and MeCP2.Neuromolecular medicine · 2014Review
- miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions.Nucleic acids research · 2014Article
- Extracellular chromosome 21-derived microRNAs in euploid & aneuploid pregnancies.The Indian journal of medical research · 2013Article
- New innovations: therapeutic opportunities for intellectual disabilities.Annals of neurology · 2013Review
- Defective thymic progenitor development and mature T-cell responses in a mouse model for Down syndrome.Immunology · 2013Article
Corrections and comments
- Retraction · 2013-02-08Falsification/Fabrication of Image · Investigation by ORI ·
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- Retracted
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. Bioinformatic annotation has established that human chromosome 21 (Hsa21) harbors five microRNA (miRNAs) genes: miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. Our laboratory recently demonstrated that Hsa21-derived miRNAs are overexpressed in DS brain and heart specimens. The aim of this study was to identify important Hsa21-derived miRNA/mRNA target pairs that may play a role, in part, in mediating the DS phenotype. We demonstrate by luciferase/target mRNA 3'-untranslated region reporter assays, and gain- and loss-of-function experiments that miR-155 and -802 can regulate the expression of the predicted mRNA target, the methyl-CpG-binding protein (MeCP2). We also demonstrate that MeCP2 is underexpressed in DS brain specimens isolated from either humans or mice. We further demonstrate that, as a consequence of attenuated MeCP2 expression, transcriptionally activated and silenced MeCP2 target genes, CREB1/Creb1 and MEF2C/Mef2c, are also aberrantly expressed in these DS brain specimens. Finally, in vivo silencing of endogenous miR-155 or -802, by antagomir intra-ventricular injection, resulted in the normalization of MeCP2 and MeCP2 target gene expression. Taken together, these results suggest that improper repression of MeCP2, secondary to trisomic overexpression of Hsa21-derived miRNAs, may contribute, in part, to the abnormalities in the neurochemistry observed in the brains of DS individuals. Finally these results suggest that selective inactivation of Hsa21-derived miRNAs may provide a novel therapeutic tool in the treatment of DS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.