Expression of miR-196a in Huntington's disease transgenic (HD) mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47500 | GEO | 2013/05/30
SECONDARY ACCESSION(S): PRJNA205896
REPOSITORIES: GEO
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Project description:We intend to screen altered genes after overexpression of miR-196a in HD transgenic mice. Two transgenic mouse lines were used in this study, including HD transgenic mice and HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. At this point, HD transgenic mice showed severve motor dysfunctions, whereas HD transgenic mice overexpressing miR-196a displayed mild motor dysfunctions. We used the striatum tissues from 2 HD transgenic mice and 3 HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. Two technique repeats were performed for each sample.
2013-05-30 | E-GEOD-47500 | biostudies-arrayexpress
Project description:Polyglutamine expansion in Huntingtin (HTT) causes its aggregation and progressive loss of striatal neurons in Huntington’s disease (HD). HD is a mostly adult-onset neurodegenerative disorder with no disease-modifying therapies. Here we found that human striatal aging is associated with a global upregulation of genes involved in translation, including the translation and proteostasis regulator PPP1R15B (R15B). We used the R15B inhibitor Raphin1 to investigate if the age-associated changes could modify HD pathology. R15B inhibition rescued early learning and late motor deficits in HDYAC128 mice. In striatal medium spiny neurons directly reprogrammed from fibroblasts of symptomatic HD patients (HD-MSNs), Raphin1 reduced the formation of mutant HTT aggregates and neuronal death. Genetic knockdown of R15B also protected HD-MSNs from neurodegeneration whereas its overexpression exacerbated disease phenotypes. Moreover, both human striatum and reprogrammed MSNs exhibited age-dependent decline of miR-196a, a microRNA that directly targets non-conserved sites in human R15B 3’UTR and overexpressing miR-196a lowered mutant HTT aggregation. This work identifies age-dependent alterations in miR-196a and its target R15B and demonstrates the therapeutic potential of reversing these changes in diverse models and readouts of HD. We propose miR-196a and R15B as disease-modifying targets in HD.
2025-12-31 | GSE264237 | GEO
Project description:Expression of miR-196a in Huntington's disease transgenic (HD) mice
| PRJNA205896 | ENA
Project description:Neural crest (NC) cells form a multipotent stem cell population specified during neurulation, which undergoes an epithelial-to-mesenchymal transition (EMT) and migrate extensively in the developing embryo, to generate numerous tissues and cell types including the craniofacial skeleton, the peripheral nervous system and pigment cells. The genetic and molecular details of neural crest specification are governed by a complex, yet still partially understood gene regulatory network (NC-GRN). In particular, the precise function of microRNAs in this network remains poorly known. MicroRNAs are short non-coding 20-22 nucleotides long RNAs which control gene expression through post-transcriptional repression. Since miRNA-196a is expressed in the developing neural and neural crest cells of Xenopus laevis embryos we here investigated miR-196a function in the NC-GRN, by knocking-down its expression using antisense morpholinos. Depletion of miR-196a revealed major neural crest and craniofacial phenotypes. These defects were preceded by the perturbed expression of key neural, neural border and neural crest markers such as sox2/3, zic1/3, pax3, sox10 and snail2. Using RNA sequencing of individual neural border and neural crest explants, we have identified a signature of genes up- and down-regulated by miR-196a and validate these with rescue experiments using a miR mimic. We show that Sox10, a predicted target of miR-196a, is lost following morpholino knockdown and rescued upon miR 196a mimic expression. Our study identifies miR-196a as a key actor of early patterning in the dorsal ectoderm, balancing the extent of immature neural plate progenitors with neural crest and placode specification, while also promoting neuron differentiation within the neural plate.
2025-10-13 | GSE289705 | GEO
Project description:miR-196a-5p is robustly upregulated under hypoxia in GBM cell lines and is highly expressed in GBM tumour samples. This study identifies the genes differentially expressed upon miR-196a-5p inhibition in A172 glioblastoma cell line under hypoxia (0.2% O2). GeneChip PrimeView Human Gene Expression Array was used to assess mRNA expression profile in response to miR-196a-5p inhibition in A172 cell line under hypoxia (0.2% O2).
2020-12-15 | GSE152575 | GEO
Project description:Hyperactivation of the PI3K/AKT pathway is observed in most NSCLCs, promoting proliferation, migration and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of the positive regulator phosphatydil-inositol-3â phosphate kinase (PIK3CA) and/or mutations of AKT1 itself. However, whereas the effects of AKT activation on mRNAs and proteins in the cell are fairly clear, the role of miRNAs as downstream targets of activated PI3K/AKT signalling is still poorly defined so far. To identify miRNAs that are targets of constitutive signalling of PI3K/AKT in lung cancer cells, we performed miRNA profiling of human lung epithelial cells expressing active mutant AKT1 (E17K), active mutant PI3KCA (E545K) or that are silenced for PTEN. We identified 28 differentially expressed miRNAs (8 up-regulated, 20 down-regulated) that were common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells. Among the 8 up-regulated miRNAs that were common to all the alterations, the miRNA most consistently up-regulated by activation of the PI3K/AKT pathway in BEAS-2B cells was miR-196a. The results reported here demonstrate that miR-196a acts as oncogene downstream the PI3K/AKT pathway, mediating the proliferative, pro-migratory and tumorigenic activity of this pathway in NSCLC cells by targeting FoxO1 and p27 expression. By adoptive expression of miR-196a in BEAS-2B cells, we demonstrated that miR-196a stimulates anchorage-dependent and -independent proliferation, migration and tumorigenicity in BEAS-2B cells. On the other hand, by use of antimir-196a in NCI-H460 cells to silence the endogenous expression of miR-196a, we demonstrate that miR-196a plays a pivotal role in mediating the stimulation of proliferation, migration and tumorigenicity induced by aberrant activation of PI3K/AKT signalling. Accordingly, we found that miR-196a was significantly overexpressed in human NSCLC-derived cell lines (n=6) and primary lung cancer samples (n=28). Finally, based on predicted binding sites for miR-196a by microRNA analysis software, we found that miR-196a affects protein levels of FoxO1 and p27 in NSCLC cells.
2016-06-13 | E-MTAB-4263 | biostudies-arrayexpress
Project description:The impact of a SNP (rs11614913) in miR-196a-2 was examined by introducing expression vectors containing both the common and variant forms of the miRNA precursor.
2009-06-08 | GSE15576 | GEO
Project description:Annexin A1 (ANXA1) is a Ca2+-binding protein involved in pancreatic cancer (PC) progression. It is able to mediate cytoskeletal organization maintaining a malignant phenotype. ANXA1 Knock-Out (KO) MIA PaCa-2 cells partially lost their migratory and invasive capabilities and also the metastatization process is affected in vivo. Here, we investigated the microRNA (miRNA) profile in ANXA1 KO cells. The analysis of the modification in miRNA expression remarked the significant involvement of ANXA1 in PC progression. In this study, we focused on miR-196a which is a well known oncogenic factor in several tumour models and it appeared down-modulated in absence of ANXA1. Furthermore, both ANXA1 and miR-196a are able to trigger the mechanisms of the epithelial to mesenchymal transition (EMT). Our results show that the reintroduction of miR-196a through the mimic sequence restored the early aggressive phenotype of MIA PaCa-2. Then, ANXA1 seems to support the expression of miR-196a and its role. On the other hand, this miRNA is able to mediate some of protein functions in PC progression. This work elucidates the correlation between ANXA1 and specific miRNA sequences, particularly miR-196a, and provides new knowledge about the protein intracellular role.
2018-08-31 | E-MTAB-6599 | biostudies-arrayexpress
Project description:Skeletal muscle atrophy is one of the critical issues which elderly people face. The precise mechanism underlying muscle atrophy during aging is not fully understood. In order to identify miRNA whose expression is changed in age-associated muscle atrophy, we performed miRNA expression profiling of skeletal muscles in young and aged rats. Microarray analysis revealed differential miRNA expression in EDL and soleus muscles of aged rats compared with those of young rats. We next investigated whether the age-associated changes of miRNA expression observed in rats were recapitulated in mice and found that the expression level of miR-206 in EDL muscle and that of miR-196a in EDL and soleus muscles were respectively higher and lower in aged rodents than in young rodents. In mouse C2C12 myoblasts and myotubes, introduction of miR-196a decreased the protein level of Forkhead-box transcription factor Foxo1, a known target of miR-196a, indicating that miR-196a may regulate Foxo1 expression also in skeletal muscles. Furthermore, miR-196a overexpression exacerbated cell death caused by an exposure to hydrogen peroxide. Lastly, we demonstrated that expression of Foxo1 was elevated in EDL and soleus muscles of aged mice compared with those of young mice. These results suggest that miRNAs are involved in skeletal muscle atrophy during aging and that decreased miR-196a expression may protect skeletal muscle cells from oxidative stress in part through induction of Foxo1.
2016-08-31 | GSE70990 | GEO
Project description:The Ndr (nuclear Dbf2-related) family members are highly conserved serine/threonine protein kinases, which function in many cellular processes extending from cytokinesis to neurite outgrowth. In humans, the NDR2 gene is located in a microduplication hotspot on chromosome 12p that is associated with intellectual disabilities in several individuals. To address a putative contribution of Ndr2 overexpression to such cognitive dysfunctions we generated conditional transgenic mice overexpressing Ndr2 in postmigratory forebrain neurons. Proteomic analysis identifies several interaction partners of transgenic Ndr2 relevant to MF maturation. including the leucin-rich repeat kinase 2 (Lrrk2).
2021-07-16 | PXD026867 | Pride