The miR-17~92 microRNA cluster is a global regulator of tumor metabolism
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77010 | GEO | 2016/07/14
SECONDARY ACCESSION(S): PRJNA309248
REPOSITORIES: GEO
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Project description:miR-17-92 mediates the MYC oncogene addiction in a conditional mouse lymphoma model. To identify targets of miR-17-92 in this model, miR-17-92 was expressed in the conditional lymphoma cell lines using MSCV-puro.
2014-05-29 | GSE57507 | GEO
Project description:A network of gene regulatory factors such as transcription factors and microRNAs establish and maintain the gene expression pattern during hematopoiesis. In this network transcription factors regulate each other and are involved in regulatory loops with microRNAs.The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes for six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.
2021-09-09 | PXD018052 | Pride
Project description:Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here we show altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact in neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors causes a decrease, while its overexpression an increase of neurogenesis in the dentate gyrus, through regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects, induced by corticosterone, in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors to regulate neurogenesis and anxiety- and depression-like behaviors.
2016-12-09 | GSE83636 | GEO
Project description:miR-17-92 mediates the MYC oncogene addiction in a conditional mouse lymphoma model. To identify targets of miR-17-92 in this model, miR-17-92 was expressed in the conditional lymphoma cell lines using MSCV-puro. Both control and miR-17-92-expressing conditional lymphoma cell lines were treated with doxycycline (DOX) (20ng/ml) for 48 hours to shut off MYC expression.
2014-05-29 | E-GEOD-57507 | biostudies-arrayexpress
Project description:The microRNAs encoded by the miR-17~92 polycistron are commonly overexpressed in cancer and orchestrate a wide range of oncogenic functions. Here, we identify a novel mechanism for miR-17~92 oncogenic function through the disruption of endogenous miRNA processing. We show that upon oncogenic overexpression of the miR-17~92 primary transcript (pri-miR-17~92), the Microprocessor complex remains associated with partially processed intermediates that aberrantly accumulate. These intermediates reflect a series of hierarchical and conserved steps in the early processing of the pri-miR-17~92 transcript. Encumbrance of the Microprocessor by miR-17~92 intermediates leads to the broad, but selective, downregulation of co-expressed polycistronic miRNAs, including miRNAs derived from tumour suppressive miR-34b/c, and from the Dlk1-Dio3 polycistrons. We propose that the newly identified steps of polycistronic miR-17~92 biogenesis contribute to the oncogenic re-wiring of gene regulation networks. Our results reveal new functional paradigms for polycistronic miRNAs in cancer.
2019-05-20 | GSE130282 | GEO
Project description:Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17~92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17~92 restrained the expression of genes ‘inappropriate’ to the TFH cell subset, including the direct miR-17~92 target Rora. Removal of one Rora allele partially ‘rescued’ the inappropriate gene signature in miR-17~92-deficient TFH cells. Our results identify the miR-17~92 cluster as a critical regulator of T cell–dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program.
2013-06-30 | GSE42760 | GEO
Project description:To identify mir-17~92 targets in MNs, a set of target candidate genes from the intersection of upregulated genes found only in the mir-17~92 KO MNs that were predicted to be direct targets of mir-17~92 by TargetScan.
2015-04-14 | GSE67795 | GEO
Project description:The deletion of a single miRNA cluster, miR-17~92, is sufficient to induce primary sex reversal in XY mice. The expression of the testis determining gene, Sry, is delayed in embryonic XY miR-17~92 knockout gonads, which immediately activate the ovarian genetic program. Single cell RNA-seq analysis shows that Sertoli cell differentiation is highly reduced, delayed and unable to trigger testis differentiation. Consistent with the well-known role of miRNAs in gene regulation, the expression of target genes of miR-17~92 is not stabilized in XY mutant gonads at E11.5, affecting, in turn, the fine regulation of large gene networks involved in mammalian sex determination. Our results reveal that the miR-17~92 cluster is a novel sex-determining factor that modulates several gene networks required for accurate timing of Sry expression and Sertoli cell differentiation during testis determination and early differentiation. bulk RNA-seq, single cell RNA-seq as well as IF and other characterizations of a transgenic mice for miR-17~92 cluster
2023-07-09 | GSE225675 | GEO
Project description:The generation of myelinating cells in the central nervous system (CNS) requires the initiation of specific gene-expression programs in oligodendrocytes. We reasoned that miRNAs could play an important role in this process by regulating critical developmental genes. Microarray profiling of cultured oligodendrocytes identifies the miR-17~92 family of miRNA cluster as highly enriched miRNAs in oligodendrocytes.We specifically deleted the miR-17~92 cluster in oligodendrocytes using the 2´3´-cyclic nucleotide 3´-phosphodiesterase (CNP)-Cre mice. Absence of miR-17~92 leads to a reduction of oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocytes promotes cell proliferation by influencing Akt signalling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17~92 cluster is crucial in this process.
2010-06-01 | GSE21797 | GEO
Project description:The deletion of a single miRNA cluster, miR-17~92, is sufficient to induce primary sex reversal in XY mice. The expression of the testis determining gene, Sry, is delayed in embryonic XY miR-17~92 knockout gonads, which immediately activate the ovarian genetic program. Single cell RNA-seq analysis shows that Sertoli cell differentiation is highly reduced, delayed and unable to trigger testis differentiation. Consistent with the well-known role of miRNAs in gene regulation, the expression of target genes of miR-17~92 is not stabilized in XY mutant gonads at E11.5, affecting, in turn, the fine regulation of large gene networks involved in mammalian sex determination. Our results reveal that the miR-17~92 cluster is a novel sex-determining factor that modulates several gene networks required for accurate timing of Sry expression and Sertoli cell differentiation during testis determination and early differentiation.
2023-07-09 | GSE225676 | GEO