Differential gene regulation by miR-142-3p and miR-K10a isomiRs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Chunfa Jie
PROVIDER: E-GEOD-66489 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This study compares changes in gene expression induced by four interrelated miRNAs with similar but staggered 5'-ends: miR-142-3p, miR-142-3p-1, miR-K10a, and miR-K10a+1. miR-K10a and miR-K10a+1 are co-expressed by the Kaposi's sarcoma-associated herpesvirus.
2015-07-31 | GSE66489 | GEO
Project description:MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by inhibiting protein synthesis of target messenger RNAs (mRNAs). MicroRNA-142 (miR-142), which has tumor-suppressive properties, was functionally deleted by CRISPR/Cas9 knockout in cell lines derived from diffuse large B-cell lymphoma (DLBCL), a highly aggressive tumor that represents about 30% of non-Hodgkin lymphoma worldwide. Mutations in miR-142 affect about 20% of all cases of DLBCL. By proteome analyses, the miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in the GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. Of the deregulated proteins/genes, CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. We further show that seed-sequence mutations of miR-142 can be used to confirm potential targets and that miRNA knockout cell lines might thus be used to identify novel targets of miRNAs. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when a miRNA highly present in the RISC complex is deleted and can be replaced by other endogenous miRNAs, primary effects on gene expression may be covered by secondary layers of regulation
2023-03-10 | PXD037148 | Pride
Project description:MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs of about 22 nt in length. Uveal melanoma is the most common intraocular malignant tumor in adults. Our previous result of microarray analysis showed that miR-142-3p was distinctly downregulated in uveal melanoma cells on which miR-142-3p was speculated to have important regulatory effect. In order to better understand the function of miR-142-3p in uveal melanoma and identify its gene targets, we performed transcriptomic microarray analysis. This was done by comparing gene expression profile changes in uveal melanoma cells transfected with miR-142-3p with that transfected with a negative control.
2019-02-28 | E-MTAB-6725 | 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:miR-142-3p is highly expressed in peripheral blood mononuclear cells (PBMCs) and has been described as a hematopoietic-restricted lineage, suggesting immune functions (Chen, Li et al. 2004; Landgraf, Rusu et al. 2007; Merkerova, Belickova et al. 2008). In order to determine the roles of miR-142-3p in B lymphocytes, we over-expressed this miRNA in the Raji B-cell line using a synthetic mimic of miR-142-3p and analyzed gene expression 24 hours after the transfection. Four replicates each of miR-142-3p-mimic transfection and apparied control mimic.
2011-05-30 | E-GEOD-28456 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs, micro ribonucleic acids) are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrichsyndrome-like, protein: N-WASP), Integrin-aV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility. ROCK2, IL6ST, KLF4, PGRMC2 and ADCY9 were identified as additional targets in a subset of cell lines. Decreased matrigel invasiveness was associated with the miR-142-3p-induced expression changes. Confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy revealed a change in cell morphology as well as a reduced cell volume and size. A more cortical actin distribution and a loss of membrane protrusions were observed in cells overexpressing miR-142-3p. Luciferase activation assays confirmed direct miR-142-3p-dependent regulation of the 3'-untranslated region of ITGAV and WASL. siRNA-mediated depletion of ITGAV andWASL resulted in a significant reduction of cellular invasiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. While knockdown of WASL significantly reduced the number of membrane protrusions compared to controls, knockdown of ITGAV resulted in a decreased cell volume, indicating differential contributions of these factors to the miR-142-3p-induced phenotype. Our data identify WASL, ITGAV and several additional cytoskeleton associated molecules as novel invasion-promoting targets of miR-142-3p in breast cancer.
2015-11-16 | GSE50829 | GEO
Project description:miR-142-3p is highly expressed in peripheral blood mononuclear cells (PBMCs) and has been described as a hematopoietic-restricted lineage, suggesting immune functions (Chen, Li et al. 2004; Landgraf, Rusu et al. 2007; Merkerova, Belickova et al. 2008). In order to determine the roles of miR-142-3p in B lymphocytes, we over-expressed this miRNA in the Raji B-cell line using a synthetic mimic of miR-142-3p and analyzed gene expression 24 hours after the transfection.
2011-05-30 | GSE28456 | GEO
Project description:To identify target genes of miR-142-5p and miR-130a-3p that are involved in M2 polarization, we examined the mRNA expression profile changes after altering miR-142-5p or miR-130a-3p expression in IL-4-treated macrophages.
2014-07-12 | GSE59347 | GEO
Project description:MicroRNAs (miRs), a group of small and non-coding RNAs, negatively regulate gene expression via promoting messenger RNA (mRNA) degradation or blocking mRNA translation. Many miRs have been recognized as biomarkers or possible targets for the diagnosis or therapy of some diseases. Among them, miR-142-3p was involved in the occurrences and progression of various cardiovascular diseases. Previous studies found that miR-142-3p upregulation could ameliorate myocardial ischemia/reperfusion (I/R)-induced transdifferentiation of fibroblasts to myofibroblasts and collagen deposition. miR-142-3p-mediacted autophagy was reported as a novel mechanism towards I/R-induced cardiac injure. Besides, miR-142-3p could mitigate myocardial mitochondrial dysfunction. Thus, it is worth studying whether silencing miR-142-3p may affect the pathological and physiological functions of cardiac fibroblasts.
2024-03-27 | GSE262000 | GEO
Project description:hematopoiesis and myelopoiesis was tightly controled by microRNAs. In the zebrafish adult kidney, specific sets of genes were dysregulated in myelomonocytes or whole kidney marrow after deletion of miR-142-3p. microarrays were used to clarified the miR-142-3p regulatory network in myelopoiesis in miR-142-3p knockout zebrafish kidney and we identified distinct classes of up-regulated genes in zebrafish myelopoiesis or hematopoiesis after deletion of miR-142-3p.
2014-07-01 | GSE58944 | GEO