A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis

Fazi, Francesco; Rosa, Alessandro; Fatica, Alessandro; Gelmetti, Vania; Marchis, Maria Laura De; Nervi, Clara; Bozzoni, Irene

doi:10.1016/j.cell.2005.09.023

Cited by 935 publications

(1,000 citation statements)

References 42 publications

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“…Although NFI-A maintains miR-223 at low levels, its replacement by C/EBPa following RA differentiation, upregulates miR-223 (Fazi et al, 2005). Consistent with these data, we confirmed that miR-223 is induced significantly upon treatment with ATRA.…”

Section: Resultssupporting

confidence: 88%

“…Furthermore, the ectopic expression of miR-181a in murine hematopoietic progenitor cells led to a proliferation in the B-cell compartment (Chen et al, 2004). More recently, it has been reported that miR-223 is a key member of a regulatory circuit involving C/EBPa and NFI-A that controls granulocytic differentiation in ATRA-treated APL cell lines (Fazi et al, 2005). Little is known, however, about other miRNAs expression in ATRAtreated APL cells.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-jB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-jB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/ miR-16-1, respectively.

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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“…Transcription factors that regulate the activity of miRNA promoters have recently been described (47,48). Moreover, several miRNA have been shown to regulate the 3Ј-UTR of mRNA that encode transcription factors (49), and a circuit that sequentially involves miRNA and transcription factors in a mutual negative feedback loop has been described (48,49).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, several miRNA have been shown to regulate the 3Ј-UTR of mRNA that encode transcription factors (49), and a circuit that sequentially involves miRNA and transcription factors in a mutual negative feedback loop has been described (48,49). As for the transcription factors, it has been reported that REST inhibits miR124a expression in non-neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis

Nakamachi¹,

Kawano²,

Takenokuchi³

et al. 2009

Arthritis & Rheumatism

302

209

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Objective. To elucidate the role of microRNA (miRNA) in the pathogenesis of rheumatoid arthritis (RA), we analyzed synoviocytes from RA patients for their miRNA expression.Methods. Synoviocytes derived from surgical specimens obtained from RA patients were compared with those obtained from osteoarthritis (OA) patients for their expression of a panel of 156 miRNA with quantitative stem-loop reverse transcription-polymerase chain reaction. The miRNA whose expression decreased or increased in RA synoviocytes as compared with OA synoviocytes were identified, and their target genes were predicted by computer analysis. We used an in vitro system of enhancing the expression of specific miRNA by transfection of precursors into synoviocytes, and then we performed proliferation, cell cycle, and apoptosis assays, as well as enzyme-linked immunosorbent assays for cytokine production. The effects of transfection on predicted target protein and messenger RNA (mRNA) were then examined by Western blot analysis and luciferase reporter assay.Results. We found that miR-124a levels significantly decreased in RA synoviocytes as compared with OA synoviocytes. Transfection of precursor miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G 1 phase. We identified a putative consensus site for miR-124a binding in the 3 -untranslated region of cyclin-dependent kinase 2 (CDK-2) and monocyte chemoattractant protein 1 (MCP-1) mRNA. Induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins. Luciferase reporter assay demonstrated that miR-124a specifically suppressed the reporter activity driven by the 3 -untranslated regions of CDK-2 and MCP-1 mRNA.Conclusion. The results of this study suggest that miR-124a is a key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes.MicroRNA (miRNA) are a well-established class of small (ϳ22 nucleotides) endogenous noncoding RNAs that influence the stability and translation of messenger RNA (mRNA) (1). Using various computational and experimental approaches, hundreds of miRNA have been identified in numerous animal species. The miRNA genes are transcribed by RNA polymerase II as primary miRNA (pri-miRNA) (2,3). The RNase III enzyme Drosha then processes the nuclear pri-miRNA, yielding a ϳ70-nucleotide molecule known as precursor miRNA (pre-miRNA) (4), which is exported from the nucleus. Maturation of the pre-miRNA into miRNA is then mediated by the cytoplasmic enzyme Dicer (5), after which the mature miRNA is loaded into the RNA-induced silencing complex (RISC)

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“…In Drosophila , reciprocal negative feedback between mir-7 and its target Yan reinforces the photoreceptor differentiation induced by the EGF signal in developing eyes [73]. A similar negative feedback regulatory circuitry involving miR-223 and two transcriptional factors, NFI-A and C/EBPα, is important in human granulocytic differentiation [74]. In C. elegans , a positive feedback loop between lin-12, mir-61 , and vav-1 was reported to maximize LIN12 activity and specify the secondary vulva cell fate [75].…”

Section: Discussionmentioning

confidence: 99%

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

Kane

Vora

Padgett

et al. 2018

Fly

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Decapentaplegic (Dpp), the Drosophila homolog of the vertebrate bone morphogenetic protein (BMP2/4), is crucial for patterning and growth in many developmental contexts. The Dpp pathway is regulated at many different levels to exquisitely control its activity. We show that bantam (ban), a microRNA, modulates Dpp signaling activity. Over expression of ban decreases phosphorylated Mothers against decapentaplegic (Mad) levels and negatively affects Dpp pathway transcriptional target genes, while null mutant clones of ban upregulate the pathway. We provide evidence that dpp upregulates ban in the wing imaginal disc, and attenuation of Dpp signaling results in a reduction of ban expression, showing that they function in a feedback loop. Furthermore, we show that this feedback loop is important for maintaining anterior-posterior compartment boundary stability in the wing disc through regulation of optomotor blind (omb), a known target of the pathway. Our results support a model that ban functions with dpp in a negative feedback loop.

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A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis

Cited by 935 publications

References 42 publications

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

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