E-TABM-441
Ontology highlight
ABSTRACT:
PROVIDER: E-TABM-441 | ExpressionAtlas | 2015-11-02
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:MiR-142 is dynamically expressed and plays a regulatory role in hematopoiesis. Based on the simple observation that miR-142 levels are significantly lower in CD34+CD38- cells from blast crisis (BC) chronic myeloid leukemia (CML). CML patients compared with chronic phase (CP) CML patients (p=0.002), we hypothesized that miR-142 deficit plays a role in BC transformation. To test this hypothesis, we generated a miR-142 KO BCR-ABL (i.e., miR-142−/−BCR-ABL) mouse by crossing a miR-142−/− mouse with a miR-142+/+BCR-ABL mouse. While the miR-142+/+BCR-ABL mice developed and died of CP CML, the miR-142−/−BCR-ABL mice developed a BC-like phenotype in the absence of any other acquired gene mutations and died significantly sooner than miR-142+/+BCR-ABL CP controls (p=0.001). Leukemic stem cell (LSC)-enriched Lineage-Sca-1+c-Kit+ cells (LSKs) from diseased miR-142−/−BCR-ABL mice transplanted into congenic recipients, recapitulated the BC features thereby suggesting stable transformation of CP-LSCs into BC-LSCs in the miR-142 KO CML mouse. Single cell (sc) RNA-seq profiling showed that miR-142 deficit changed the cellular landscape of the miR-142−/−BCR-ABL LSKs compared with miR-142+/+BCR-ABL LSKs with expansion of myeloid-primed and loss of lymphoid-primed factions. Bulk RNA-seq analyses along with unbiased metabolomic profiling and functional metabolic assays demonstrated enhanced fatty acid β-oxidation (FAO) and oxidative phosphorylation (OxPhos) in miR-142−/−BCR-ABL LSKs vs miR-142+/+BCR-ABL LSKs. MiR-142 deficit enhanced FAO in miR-142−/−BCR-ABL LSKs by increasing the expression of CPT1A and CPT1B, that controls the cytosol-to-mitochondrial acyl-carnitine transport, a critical step in FAO. MiR-142 deficit also enhanced OxPhos in miR-142−/−BCR-ABL LSKs by increasing mitochondrial fusion and activity. As the homeostasis and activity of LSCs depend on higher levels of these oxidative metabolism processes, we then postulate that miR-142 deficit is a potentially druggable target for BC-LSCs. To this end, we developed a novel CpG-miR-142 mimic oligonucleotide (ODN; i.e., CpG-M-miR-142) that corrected the miR-142 deficit and alone or in combination with a tyrosine kinase inhibitor (TKI) significantly reduced LSC burden and prolonged survival of miR-142−/−BCR-ABL mice. The results from murine models were validated in BC CD34+CD38- primary blasts and patient-derived xenografts (PDXs). In conclusion, an acquired miR-142 deficit sufficed in transforming CP-LSCs into BC-LSCs, via enhancement of bioenergetic oxidative metabolism in absence of any additional gene mutations, and likely represent a novel therapeutic target in BC CML.
2023-01-13 | ST002446 | MetabolomicsWorkbench
Project description:Expression profiling of muscle tissue isolated from WT, miR-22 KO, miR-22/ERalpha KO, and miR-22KO/muscle specific ERalphaKO
2017-03-13 | E-MTAB-3518 | biostudies-arrayexpress
Project description:To gain insight into how miR-142 deficit drives a BC-like transformation, we performed RNA-seq on bone marrow (BM) Lin-Sca-1+c-Kit+ cells (LSKs) harvested from normal miR-142+/+ (wt) and miR-142−/− (miR-142 KO) mice, as well as from leukemic miR-142+/+ BCR-ABL (CP CML) and miR-142−/− BCR-ABL (BC CML) mice, two weeks after BCR-ABL induction. We then performed gene expression profiling analysis using data obtained from RNA-seq of 24 samples of LSK cells from 4 mouse strains (KO vs WT, KO CML vs CML).
2022-11-01 | GSE216794 | GEO
Project description:Liver transcriptome profiling of liver specific miR-122 knockout (miR-122loxP/loxP Alb-Cre) and control (miR-122loxP/loxP) male mice. Expression profile of several hundred mRNAs that include miR-122 targets were altered in miR-122 KO livers. Loss of miR-122 in the germ line resulted in significant changes in hepatic gene expression profile. Among the upregulated genes many are direct targets of miR-122
2012-03-03 | GSE20610 | GEO
Project description:Purpose: Determine the differential gene expression pattern between wildtype, Pkd2-KO and Pkd2-miR-214 KO mice Methods: kidney mRNA profiles of Pkd2-KO and Pkd2-mir-214-KO mice was sequenced with N of 3 in each group Results: 972 differentially expressed transcripts were identified between Pkd2-KO kidneys and Pkd2-miR-214-KO kidneys Conclusion: Deletion of miR-214 promotes interstitial inflammation in mouse models of ADPKD
2019-09-25 | GSE137945 | GEO
Project description:MiR-146a is an important regulator of innate inflammatory responses and is also implicated in cell death and survival. Here, we identified microglia as the main cellular source of miR-146a among mouse CNS resident cells. We further characterized the phenotype of miR-146a KO microglia cells during in vivo demyelination induced by cuprizone (CPZ) and found reduced number of CD11c+ microglia in the KO compared to WT mice. Microglia were also isolated from the brain, and the proteome was analyzed by liquid chromatography mass spectrometry.
2020-06-29 | PXD015939 | Pride
Project description:Liver transcriptome profiling of liver specific miR-122 knockout (miR-122loxP/loxP Alb-Cre) and control (miR-122loxP/loxP) male mice. Expression profile of several hundred mRNAs that include miR-122 targets were altered in miR-122 KO livers. Loss of miR-122 in the germ line resulted in significant changes in hepatic gene expression profile. Among the upregulated genes many are direct targets of miR-122 GSM517838-GSM517847: Liver transcriptome profiling of liver specific miR-122 knockout and control male mice. Total liver RNA from 8 week old five control and five liver-specific miR-122 knock out male mice (C57/BL6J background) GSM791601-GSM791604: Liver transcriptome profiling of germ-line miR-122 knockout and control male mice. Liver RNA from 5 week old control (floxed) and miR-122KO mice were analyzed by mouse whole transcriptome profiling.
2012-03-03 | E-GEOD-20610 | biostudies-arrayexpress
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.
2017-03-29 | MSV000080762 | MassIVE
Project description:Genome-wide analysis of Jarid2, Suz12, and c-Maf binding and H3K27me3 profiling in miR-155 KO and WT Th17 performed by ChIP-seq. We found that Jarid2 and c-Maf is differentially expressed in absence of miR-155 and they compete for binding to the Il22 promoter. We highlight targets of Jarid2 and Suz12 in miR-155 KO Th17 cells that are epigenetically silenced by increased H3K27me3 status. Furthermore, genome-wide analysis through Suz12 ChIP-exo in WT and Jarid2fl/fl;CD4cre Th17 reveals defects in PRC2 recruitment in abscence of Jarid2 that results in derepression of genes in Th17 cells. Thus, one main function of miR-155 is to curb epigenetic silencing by targeting Jarid2. Examination of Jarid2, Suz12, c-Maf binding and H3K27me3 changes in miR-155 KO and WT Th17.
2014-06-01 | E-GEOD-47528 | biostudies-arrayexpress
Project description:We conducted expression profiling of white adipose tissue isolated from WT and miR-22 KO animals. The main work is analysis of the miR-22 function in striated muscle. White adipose tissue (WAT) was analyzed to look at effects in WAT, as that might be induced by metabolic changes in skeletal muscle.
2017-03-13 | E-MTAB-5409 | biostudies-arrayexpress