Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA253827 | ENA |
REPOSITORIES: ENA
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Project description:The oncomir microRNA-125b (miR-125b) is up-regulated in a variety of human neoplastic blood disorders and constitutive up-regulation of miR-125b in mice can promote myeloid and B cell leukemia. We found that miR-125b promotes myeloid and B cell neoplasm by inducing tumorigenesis in hematopoietic progenitor cells. Our study demonstrates that miR-125b induces myeloid leukemia by enhancing myeloid progenitor output from stem cells as well as inducing immortality, self-renewal, and tumorigenesis in myeloid progenitors. Through functional and genetic analyses, we demonstrated that miR-125b induces myeloid and B cell leukemia by inhibiting IRF4 but through distinct mechanisms; it induces myeloid leukemia through repressing IRF4 at the mRNA level without altering the genomic DNA and induces B cell leukemia via genetic deletion of the gene encoding IRF4. The cancer myeloid (Cd11b+ sorted) and B cells (CD19+ sorted) were harvested from mice that over-express miR-125b. The genomic DNA was extracted from these cells. A total of 4 cancer samples (Two myeloid cancer samples and two B cell cancer samples) were analyzed. As control, genomic DNA from cells harvested from healthy C57bl/6 mice were harvested.
2014-06-27 | E-GEOD-58900 | biostudies-arrayexpress
Project description:The oncomir microRNA-125b (miR-125b) is up-regulated in a variety of human neoplastic blood disorders and constitutive up-regulation of miR-125b in mice can promote myeloid and B cell leukemia. We found that miR-125b promotes myeloid and B cell neoplasm by inducing tumorigenesis in hematopoietic progenitor cells. Our study demonstrates that miR-125b induces myeloid leukemia by enhancing myeloid progenitor output from stem cells as well as inducing immortality, self-renewal, and tumorigenesis in myeloid progenitors. Through functional and genetic analyses, we demonstrated that miR-125b induces myeloid and B cell leukemia by inhibiting IRF4 but through distinct mechanisms; it induces myeloid leukemia through repressing IRF4 at the mRNA level without altering the genomic DNA and induces B cell leukemia via genetic deletion of the gene encoding IRF4.
2014-06-27 | GSE58900 | GEO
Project description:To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we preceded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental 32Dclone3 myeloid cell line and that ectopically expressing miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Compare the gene expression level in vector transduced 32Dclone3 cells with that in miR-125b transduced 32Dclone3 cells.
2012-04-04 | E-GEOD-37018 | biostudies-arrayexpress
Project description:To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we proceeded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental NB4 myeloid cell line and that transiently transfected with miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Compare the gene expression levels in miR control transfected cells with that in miR-125b transfected NB4 cells.
2012-04-06 | E-GEOD-37061 | biostudies-arrayexpress
Project description:To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we proceeded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental NB4 myeloid cell line and that transiently transfected with miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells.
2012-04-06 | GSE37061 | GEO
Project description:To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we preceded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental 32Dclone3 myeloid cell line and that ectopically expressing miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells.
2012-04-05 | GSE37018 | GEO
Project description:We report here the expression profile of microRNAs in human neuronal differentiation in the neuroblastoma cell line SH-SY5Y. Six microRNAs were significantly upregulated during differentiation induced by all-trans¬-retinoic acid and brain-derived neurotrophic factor. We demonstrated that ectopic expression of either miR-124a or miR-125b increases the percentage of differentiated SH-SY5Y cells with neurite outgrowth. Subsequently, we focused our functional analysis on miR-125b and demonstrated the important role of this miRNA in both spontaneous and induced differentiation of SH-SH5Y cells, based on neurite outgrowth and neuronal marker expression. In human neural progenitor ReNcell VM cells, miR-125b is also upregulated during differentiation and miR-125b ectopic expression significantly promotes neurite outgrowth. To identify the targets of miR-125b regulation, we profiled the global changes in gene expression following miR-125b ectopic expression in SH-SY5Y cells. miR-125b represses 164 genes that contain the seed match sequence of the microRNA and/or predicted to be direct targets of miR-125b by conventional methods. Pathway analysis suggests that a subset of miR-125b-repressed targets antagonize neuronal genes in several neurogenic pathways, thereby mediating the positive effect of miR-125b on neuronal differentiation. We have further validated the binding of miR-125b to the microRNA response elements of ten selected targets. Together, we report here for the first time the important role of miR-125b in human neuronal differentiation. Keywords: mir125-OE/mir-scrambled control comparison & mir125-KD/mir-scrambled control comparsion
2009-02-12 | GSE14787 | GEO
Project description:Although regulation of stem cell homeostasis by miRNAs is well studied, it is unclear how individual miRNAs, genomically encoded within an organized polycistron, can interact to induce an integrated phenotype. miR-99a/100, let-7 and miR-125b paralogues are encoded in two tricistrons on human chromosome 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Integrative analysis of global gene expression profiling, miRNA target prediction and pathway architecture revealed that miR-99a/100, let-7 and miR-125b functionally converge at the combinatorial block of the TGFM-NM-2 pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, downregulation of tumor suppressor genes APC/APC2 stabilizes active M-NM-2-Catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFM-NM-2 signaling the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo, while favoring megakaryocytic differentiation. We lentivirally transduced cord blood CD34+-hematopoietic stem and progenitor cells (CB-HSPCs) to ectopically express miR-125b-2, miR-99a, let-7c or miR-99a~125b-2 and cultured them in megakaryocytic differentiation medium for 7 days.
2014-03-28 | E-GEOD-56335 | biostudies-arrayexpress
Project description:Transcriptional profiling of breast cancer cells comparing pre-control transfected cells with cells transfected with pre-miR-125b. We searched for miR-125b targets by systematic screening of mRNA profiling of pre-miR-125b transfected MCF-7 cells and MDA-MB-435 cells. Two-condition experiment, pre-miR-125b Transfected vs. pre-control Transfected MCF-7 cells. One replicate per array.
2010-06-25 | E-GEOD-22546 | biostudies-arrayexpress
Project description:Sirtuins (SIRT) are NAD-dependent protein deacteylases and function in cellular metabolism, stress resistance, proliferation and disease. For SIRT7, a role in ribosomal gene transcription is proposed, but its function in cancer is currently unknown. In this study, we showed that SIRT7 expression was up-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that high expression of SIRT7 was associated with poor prognosis of HCC patients. Notably, inactivation of SIRT7 by siRNA suppressed tumor cell growth and caused G1/S cell cycle arrest in liver cancer cells. This treatment restored p21WAF1/Cip1 activity, induced Beclin-1 and autophagic gene expression and repressed cyclin D1. To explore mechanisms in SIRT7 regulation, microRNA (miRNA) profiling was carried out. This identified five significantly down-regulated miRNAs in HCC. Bioinformatic analysis of target sites and ectopic expression in HCC cells evidenced miR-125a-5p and miR-125b to suppress SIRT7 and cyclin D1 expression and to induce p21WAF1/Cip1-dependent G1 cell cycle arrest. Furthermore, treatment of HCC cells with 5-aza-2’-deoxycytidine or ectopic expression of wild-type but not mutated p53 restored miR-125a-5p and miR-125b expression and inhibited tumor cell growth to suggest their regulation by promoter methylation and p53 activity. To evidence clinical significance of these findings, mutations in the DNA binding domain of p53 and promoter methylation of miR-125b were investigated. Four out of nine patients with induced SIRT7 carried mutations in p53 gene and one patient showed hypermethylation of miR-125b promoter region. Conclusion: Our findings suggest that oncogenic potential of SIRT in hepatocarcinogenesis and that a regulatory loop is proposed whereby SIRT7 inhibits transcriptional activation of p21WAF1/Cip1 via repression of miR-125a-5p and miR-125b. This makes SIRT7 a promising target in cancer therapy.
2012-09-30 | GSE39678 | GEO