Targets of miR-212/132 in doxorubicin-induced cardiotoxicity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE121965 | GEO | 2018/12/29
REPOSITORIES: GEO
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Project description:Targets of miR-212/132 in doxorubicin-induced cardiotoxicity
| PRJNA512080 | ENA
Project description:miR-132 and miR-212 are structurally-related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same non-coding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/212 double knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/212 double knockout line explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/212 deletion increased the expression of 1,138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that, these two genes may function in a complex, non-redundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders
2016-03-01 | GSE73413 | GEO
Project description:Transcriptomic profiling of miR-132/212-deficient and WT CD4 T cells isolated from spleens of L donovani infected mice (d28) to determine the effects of miR-132/212 on CD4 T cell activation in vivo. This was combined by transcriptomic analysis of early stage in vitro activated WT and miR-132/212-deficient CD4 T cells to identify direct miR-132/212 targets in CD4 T cells.
2019-03-22 | GSE125268 | GEO
Project description:To identify the target of miR-212, miR-132 and HIC1, we have employed whole genome microarray expression profiling on the human breast cancer MCF7 cells. To generate miR-212/132 or HIC1 inducible MCF7 cells, doxycycline-dependent miR-212/132 or HIC1 gene expression system was used. Either Tet-ON miR-212/132 MCF7 or Tet-ON HIC1 MCF7 were treated with 1μg/ml of Doxycycline for 36 hours with EMEM containing 0.01 mg/ml bovine insulin and 10% FCS. Two independent experiments were performed.
2014-07-29 | E-GEOD-37945 | biostudies-arrayexpress
Project description:MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the pre-pro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in increased B cell output under non-homeostatic conditions. We find that miR-212/132 regulates B lymphopoiesis by targeting the transcription factor SOX4. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from over-expression of miR-132 alone. In addition, we show that the expression of miR-132 in cells that are prone to spontaneous B cell cancers can have a protective effect on cancer development. We have thus uncovered a novel regulator of B cell lineage specification that may potential applications in B cell cancer therapy
2015-09-01 | GSE66882 | GEO
Project description:To identify the target of miR-212, miR-132 and HIC1, we have employed whole genome microarray expression profiling on the human breast cancer MCF7 cells.
2014-07-29 | GSE37945 | GEO
Project description:MicroRNAs are critical post-transcriptional regulators of hematopoietic cell-fate decisions, though little remains known about their role in aging hematopoietic stem cells (HSCs). The microRNA-212/132 cluster (miR-212/132) is enriched in HSCs and is up-regulated during hematopoietic aging. Both over-expression and deletion of microRNAs in this cluster leads to inappropriate hematopoiesis with age. Enforced expression of miR-132 in the bone marrow compartment of mice led to rapid HSC cycling followed by their depletion. A genetic deletion of the miR-212/132 cluster in mice resulted in HSCs that had altered cycling, function, and survival in response to growth factor starvation. We found that miR-212/132 exerts its effect on aging HSCs by targeting the transcription factor FOXO3, a known aging associated gene. Our data demonstrates that miR-212/132 plays a role in maintaining balanced hematopoietic output by buffering FOXO3 expression. We have thus identified a novel target that may play a role in age-related hematopoietic defects.
2015-06-01 | GSE66352 | GEO
Project description:MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the pre-pro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in increased B cell output under non-homeostatic conditions. We find that miR-212/132 regulates B lymphopoiesis by targeting the transcription factor SOX4. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from over-expression of miR-132 alone. In addition, we show that the expression of miR-132 in cells that are prone to spontaneous B cell cancers can have a protective effect on cancer development. We have thus uncovered a novel regulator of B cell lineage specification that may potential applications in B cell cancer therapy RNA-seq of wild-type and microRNA-212/132 knock-out B-cells after IgM stimulation
2015-09-01 | E-GEOD-66882 | biostudies-arrayexpress
Project description:miR-132 and miR-212 are structurally-related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same non-coding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/212 double knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/212 double knockout line explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/212 deletion increased the expression of 1,138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that, these two genes may function in a complex, non-redundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders Hippocampal mRNA was isolated from CaMKII-Cre::miR-132/212f/f, tTA::miR132, and tTA::miR212 animals, as well as their respective nontransgenic controls. cDNA from six animals was pooled into three independent biological replicates for each. Libraries were prepared according to the Illumina TruSeqTM Sample Preparation Guide and sequenced using an Illumina Genome Analyzer II. Sequences were aligned to the UCSC mm9 reference genome using Bowtie v0.12.7 and custom R scripts. The sequence data have been submitted to the NCBI Short Read Archive with accession number in progress. Relative abundance was measured in Fragments Per Kilobase of exon per Million fragments mapped using Cufflinks v1.2.
2016-03-01 | E-GEOD-73413 | biostudies-arrayexpress
Project description:The abnormal regulation of amyloid-b (Ab) metabolism (e.g., production, cleavage, clearance) plays a central role in Alzheimer’s disease (AD). Among endogenous factors believed to participate in AD progression are the small regulatory non-coding microRNAs (miRs). In particular, the miR-132/212 cluster is severely reduced in the AD brain. In previous studies we have shown that miR-132/212 deficiency in mice leads to impaired memory and enhanced Tau pathology as seen in AD patients. Here we demonstrate that the genetic deletion of miR-132/212 promotes Ab deposition and amyloid (senile) plaque formation in triple transgenic AD (3xTg-AD) mice. Using RNA-Seq and bioinformatics, we identified genes of the miR-132/212 network with documented roles in the regulation of Ab metabolism, including Tau, Mapk, and Sirt1.
2016-07-17 | GSE84481 | GEO