Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Gilicze, Anna; Wiener, Zoltán; Tóth, Sára; Buzás, Edit I.; Pállinger, Éva; Falcone, Franco H.; Falus, András

doi:10.1155/2014/870267

Cited by 38 publications

(27 citation statements)

References 61 publications

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“…KSRP has been shown to regulate mRNA stability, mRNA localization, and mRNA translation in different systems 21 – 23 . Nevertheless, here we focused on its recently reported roles in miRNA processing because several miRNAs regulate myeloid differentiation 17 , 24 . A comparative analysis of miRNA transcripts expressed in KSRP-overexpressing THP-1 cells was performed by poly(A)-enriched RNA sequencing (primary miRNA transcripts) and small RNA sequencing (mature miRNA transcripts) to determine whether KSRP negatively regulates monocyte/granulocyte differentiation by modulating miRNA biogenesis (Fig.…”

Section: Resultsmentioning

confidence: 99%

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression

Zhao

Wang

et al. 2017

Nat Commun

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RNA-binding proteins (RBPs) integrate the processing of RNAs into post-transcriptional gene regulation, but the direct contribution of them to myeloid cell specification is poorly understood. Here, we report the first global RBP transcriptomic analysis of myeloid differentiation by combining RNA-seq analysis with myeloid induction in CD34+ hematopoietic progenitor cells. The downregulated expression of the KH-Type Splicing Regulatory Protein (KSRP) during monocytopoiesis and up-regulated expression during granulopoiesis suggests that KSRP has divergent roles during monocytic and granulocytic differentiation. A further comparative analysis of miRNA transcripts reveals that KSRP promotes the biogenesis of miR-129, and the expression patterns and roles of miR-129 in myeloid differentiation are equivalent to those of KSRP. Finally, miR-129 directly blocks the expression of Runt Related Transcription Factor 1 (RUNX1), which evokes transcriptional modulation by RUNX1. Based on our findings, KSRP, miR-129, and RUNX1 participate in a regulatory axis to control the outcome of myeloid differentiation.

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Section: Resultsmentioning

confidence: 99%

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression

Zhao

Wang

et al. 2017

Nat Commun

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“…MiR-223 expression is not confined to the MDSCs. In humans, miR-223 is expressed in granulocyte subsets [8, 12], and its expression decreases during monocytes/macrophage differentiation [29]. …”

Section: Introductionmentioning

confidence: 99%

Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis

et al. 2016

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Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects. To gain mechanistic insights, we interrogated the EAE model. MiR-223 knock out (miR-223−/−) mice developed less severe EAE with increased MDSC numbers in the spleen and spinal cord compared to littermate controls. MiR-223−/− MO-MDSCs suppressed T cell proliferation and cytokine production in vitro and EAE in vivo more than wild-type MO-MDSCs. They also displayed an increased expression of critical mediators of MDSC suppressive function, Arginase-1(Arg1), and the signal transducer and activator of transcription 3 (Stat3), which herein, we demonstrate being an miR-223 target gene. Consistently, MDSCs from MS patients displayed decreased STAT3 and ARG1 expression compared with healthy controls, suggesting that circulating MDSCs in MS are not only reduced in numbers but also less suppressive. These results support a critical role for miR-223 in modulating MDSC biology in EAE and in MS and suggest potential novel therapeutic applications.

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“…15 miR-652 has been reported to be a factor that mainly functions in myeloid regulation. 16 In addition, miR-652 can suppress the epithelial-mesenchymal transition of pancreatic cancer cells in acidic microenvironment conditions by targeting ZEB1. 17 miR-652-3p promotes non-small-cell lung cancer proliferation and metastasis by directly targeting the lethal giant larvae 1.…”

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confidence: 99%

Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression

et al. 2017

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Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18 deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results reveal a crucial role for circRNA in regulating mitochondrial dynamics and apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic avenue for cardiovascular diseases.

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Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Cited by 38 publications

References 61 publications

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression

Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis

Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression

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