Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA134783 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We found frequent epigenetic silencing of microRNA-34b/c in human colorectal cancer. Introduction of miR-34b/c into a colorectal cancer cell line induced significant changes in gene expression profile. We also found overlap between the genes downregulated by miR-34b/c and those downregulated by DAC. Keywords: dose response A colorecal cancer cell line HCT116 was transfected with miR-34b or -c precursor or negative control. Also, HCT116 was treated with 5-aza-2'-deoxycytidine (DAC) or mock. Genes up- or downregulated by miR-34b/c and those by DAC was compared.
2008-04-30 | E-GEOD-10455 | biostudies-arrayexpress
Project description:The miR-34 family of microRNAs consisting of miR-34a, miR-34b and miR-34c are tumour suppressors. The annotated human miR-34b-5p has one additional base at the 5’ end of the common miR-34 family seed sequence, compared to miR-34a-5p and miR-34c-5p. This extra base results in a shift of the seed sequence, which would affect the target gene repertoire and have functional consequences. During our studies of miR-34 functions, we investigated the precise sequence of mature miR-34b-5p in human cells by deep sequencing. We found that a miR-34b-5p without the extra base was the predominant form in both non-malignant and malignant cells derived from several human tissues, indicating that the miR-34b annotation is misleading. We evaluated the functional implications of the seed shift, by comparing the effect of mimics representing the alternative miR-34b-5p sequences in MDA-MB-231 cells. In contrast to the annotated miR-34b, the endogenously expressed miR-34b displayed tumour suppressive characteristics in vitro similarly to miR-34c. These data demonstrate the importance of determining the precise sequence of a mature microRNA before exploring miRNA functions.
2017-09-14 | GSE98601 | GEO
Project description:We found frequent epigenetic silencing of microRNA-34b/c in human colorectal cancer. Introduction of miR-34b/c into a colorectal cancer cell line induced significant changes in gene expression profile. We also found overlap between the genes downregulated by miR-34b/c and those downregulated by DAC. Keywords: dose response
2008-04-30 | GSE10455 | GEO
Project description:We used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs. Each donors were transfected with pre-miR-Negative control, pre-miR-449a and pre-miR-449b. The donors 3 and 4 were morever transfected with pre-miRs-34 (34a, 34b-5p, 34c-5p).
2011-06-06 | E-GEOD-22143 | biostudies-arrayexpress
Project description:Multiciliated cells (MCCs) possess multiple motile cilia on the cell surface and are widely distributed throughout the vertebrate body to perform important physiological functions by regulating fluid movement in the intercellular space. However, neither their function during organ development nor the molecular mechanisms underlying multiciliogenesis are yet well understood. We aim to study the function of miR-34b in multiciliogenesis. We used microarrays to study the global gene expression change in multiciliated cells after miR-34b knockdown. Multiciliated cells were isolated from 3 dpf control embryos (injected with control morpholino) and miR-34b morphants (injected with miR-34b morpholino) for RNA extraction and hybridization on Affymetrix microarrays. Two independent sets of biological replicates were used.
2013-05-11 | E-GEOD-46844 | biostudies-arrayexpress
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:Multiciliated cells possess multiple motile cilia on the cell surface and are widely distributed throughout the vertebrate body to perform important physiological functions by regulating fluid movement in the intercellular space. However the molecular mechanisms underlying multiciliogenesis are not well understood. Although dysregulation of members of the miR-34 family plays a critical role in the progression of various cancers, the physiological function of miR-34b, especially in regulating multiciliogenesis, is largely unknown. Here we focus on the multiciliated cells in the zebrafish kidney to study whether and how miR-34b regulate multiciliogenesis. We performed genome-wide gene expression profiling of zebrafish kidney multiciliated cells in the absence (miR-34b morpholino) or presence of miR-34b (control morpholino). RNA samples for microarray gene expression profiling were collected at 3 days post fertilization.
2013-06-14 | E-MEXP-3893 | biostudies-arrayexpress
Project description:miR-34a and miR-34b/c genes are frequently epigenetically silenced in primary CRCs. However, the in vivo relevance of miR-34a/b/c for suppression of intestinal tumor formation has not been analyzed by genetic approaches. ApcMin/+ mice with deletion of the miR-34a and miR-34b/c genes were generated and analyzed. The mRNA expression profiles of intestinal adenomas with and without functional miR-34a/b/c genes were compared.
2017-05-28 | GSE84138 | GEO
Project description:To examine the role of CREB overexpression in hematopoiesis, we created a model of leukemia in zebrafish by overexpressing the human CREB in the myeloid hematopoietic lineage. Whole transcriptome analysis of kidney-marrow revealed 171 genes differently expressed between CREB- and control-zebrafish (five per group). Interestingly, the integration of this signature with human deposited data revealed that this tumor resembled a human AML at transcriptome level.
2016-12-06 | GSE71270 | GEO
Project description:The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feed-forward loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, we show that Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
2017-06-14 | PXD004192 | Pride