MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation

Hashimi, Sara T.; Fulcher, Jennifer A.; Chang, Margaret H.; Gov, Lanny; Wang, Shuo; Lee, Benhur

doi:10.1182/blood-2008-09-179150

Cited by 258 publications

(207 citation statements)

References 43 publications

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“…As miR-34a, which is a direct target of p53, has been well-characterized as an apoptosis executor through direct targeting of apoptosis-related genes including bcl-2, it is very likely that the distinctive regulation of miR-34a accounts for the differential apoptosis mechanism observed between MSCs and De-MSCs on oxidative stress. Conversely, a role for miR-34a in cell differentiation has been recently reported [63][64][65]. Intriguingly, Aranha et al has demonstrated that overexpression of miR-34a increases the proportion of postmitotic neurons in distinct models of neural differentiation including mouse embryonic stem cells and neural stem cells.…”

Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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“…MiR-34a has also been shown to be a negative regulator of the Wnt pathway based on its targeting of WNT1. 131,132 In HCC where miR-34 is downregulated, repression of WNT1 is released. Moreover, in addition to invasion and metastasis, the Wnt/b-catenin pathway is also important for maintaining stemness.…”

Section: 3mentioning

confidence: 99%

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

et al. 2014

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MicroRNAs (miRNAs) constitute a large class of short RNAs (e.g., 20-24 nucleotides in length), whose main function is to posttranscriptionally regulate the expression of protein-coding genes. Their importance in tumorigenesis has been demonstrated over the past decade, and correspondingly, they have emerged as potential therapeutic molecules and targets. Liver cancer is one of the most common neoplastic diseases worldwide, and it currently has a poor prognosis owing to largely ineffective therapeutic options. Liver cancer is also an excellent model for testing miRNA-based therapy approaches as it can be easily targeted with the systemic delivery of oligonucleotides. In recent years, the role of miRNAs in hepatocellular carcinoma (HCC) has been established with molecular studies and the development of animal models. These studies have also provided the basis for evaluating the therapeutic potential of miRNAs, or anti-miRNAs. In general, the safety of miRNAs has been proven and antitumor activity has been observed. Moreover, because of the absence or presence of mild side effects, the prophylactic use of miRNA-based approaches may be foreseen.

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“…Mature miRNAs, ~22-25 nucleotides in length, downregulate mRNA expression through the assembly of a miRNA-induced silencing complex known as RISC, which binds complementary sequences in target mRNAs and subsequently causes catalytic cleavage or transcriptional repression of target mRNAs (6). Several miRNAs were demonstrated to regulate downstream inflammatory responses by directly targeting genes encoding molecules that are secreted by or are expressed on the surface of immune cells (7)(8)(9). Specific miRNAs are capable of targeting genes that control epige netic pathways.…”

Section: Introductionmentioning

confidence: 99%

microRNA expression profiling and bioinformatic analysis of dengue virus-infected peripheral blood mononuclear cells

Zhang

et al. 2013

Molecular Medicine Reports

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Abstract. Dengue virus (DENV) causes self-limiting dengue fever (DF), severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). It is generally considered that cytokine storm leads to the increased plasma leakage characteristic of DHF/DSS. In the present study, peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of healthy volunteers and infected with DENV serotype 2 (DENV2). Culture supernatants of DENV2-infected and -uninfected PBMCs were analyzed using a human cytokine array. Between a 6-12 h post-infection, levels of CCL5, IL-6 and IL-8 were markedly elevated, while those of TNF-α decreased. Total RNA isolated from these PBMCs was analyzed by human miRNA microarray to identify differentially expressed microRNAs (miRNAs). Quantitative reverse transcription polymerase chain reaction was used to validate 11 upregulated and 4 downregulated miRNAs. Sanger mibase, miRanda and TargetScan were used to identify 261 common predicted genes. Databases were used to identify homologous sequences on mRNAs of putative target genes that may be directly bound by the miRNAs identified. We found that cytokines and epigenetic regulators may be putative target genes of these miRNAs. Using ingenuity pathway analysis, we noted that canonical pathways, including biological regulation, may be modulated by these miRNAs.

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MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation

Abstract: MicroRNAs

Cited by 258 publications

References 43 publications

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

microRNA expression profiling and bioinformatic analysis of dengue virus-infected peripheral blood mononuclear cells

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