miRviewer: a multispecies microRNA homologous viewer

Kiežun, Adam; Artzi, Shay; Modai, Shira; Volk, Naama; Isakov, Ofer; Shomron, Noam

doi:10.1186/1756-0500-5-92

Cited by 72 publications

(55 citation statements)

References 18 publications

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“…23 Interestingly, altered plasma levels of endothelial-rich miRNAs, for example, miR-191 or miR-126 is reported to reflect underlying endothelial dysfunction in diabetes mellitus. 16 miR-191 is coexpressed with the miR-191/425 cluster which is highly conserved in higher eukaryotes 24 and our plasma miRNA profiles also confirm a unidirectional changes in circulating plasma levels of both clustered miRNAs from patients with diabetes mellitus with impaired wound healing compared with diabetics with no chronic wound. miR-200b is a known hypoxia-sensitive miRNA that induces angiogenesis in hypoxic dermal cells.…”

Section: Discussionsupporting

confidence: 56%

Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines

Dangwal

Stratmann

Bang

et al. 2015

ATVB

131

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Objective— MicroRNAs (miRNA/miR) are stably present in body fluids and are increasingly explored as disease biomarkers. Here, we investigated influence of impaired wound healing on the plasma miRNA signature and their functional importance in patients with type 2 diabetes mellitus. Approach and Results— miRNA array profiling identified 41 miRNAs significantly deregulated in diabetic controls when compared with patients with diabetes mellitus–associated peripheral arterial disease and chronic wounds. Quantitative real-time polymerase chain reaction validation confirmed decrease in circulating miR-191 and miR-200b levels in type 2 diabetic versus healthy controls. This was reverted in diabetic subjects with associated peripheral arterial disease and chronic wounds, who also exhibited higher circulating C-reactive protein and proinflammatory cytokine levels compared with diabetic controls. miR-191 and miR-200b were significantly correlated with C-reactive protein or cytokine levels in patients with diabetes mellitus. Indeed, proinflammatory stress increased endothelial- or platelet-derived secretion of miR-191 or miR-200b. In addition, dermal cells took up endothelial-derived miR-191 leading to downregulation of the miR-191 target zonula occludens-1. Altered miR-191 expression influenced angiogenesis and migratory capacities of diabetic dermal endothelial cells or fibroblasts, respectively, partly via its target zonula occludens-1. Conclusions— This study reports that (1) inflammation underlying nonhealing wounds in patients with type 2 diabetes mellitus influences plasma miRNA concentrations and (2) miR-191 modulates cellular migration and angiogenesis via paracrine regulation of zonula occludens-1 to delay the tissue repair process.

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Section: Discussionsupporting

confidence: 56%

Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines

Dangwal

Stratmann

Bang

et al. 2015

ATVB

131

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“…Moreover, this information can also be obtained by expanding the alignment of mir-155 beyond the 11 mammalian precursor sequences employing microRNAviewer (http://people.csail.mit.edu/akiezun/microRNA viewer/all_mir-155-align.html) (Supplemental Fig. S1; Kiezun et al 2012). The length of hairpin mir-155 is variable (mean = 68.3 nt) with the longest sequence (105 nt) belonging to Ornithorhynchus anatinus (oan).…”

Section: Hairpin Mir-155 Sequences In Mammalsmentioning

confidence: 99%

Rat mir-155 generated from the lncRNA Bic is ‘hidden’ in the alternate genomic assembly and reveals the existence of novel mammalian miRNAs and clusters

Uva

Sacco

Cornò

et al. 2013

RNA

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MicroRNAs (miRNAs) are a class of small noncoding RNAs acting as post-transcriptional gene expression regulators in many physiological and pathological conditions. During the last few years, many novel mammalian miRNAs have been predicted experimentally with bioinformatics approaches and validated by next-generation sequencing. Although these strategies have prompted the discovery of several miRNAs, the total number of these genes still seems larger. Here, by exploiting the species conservation of human, mouse, and rat hairpin miRNAs, we discovered a novel rat microRNA, mir-155. We found that mature miR-155 is overexpressed in rat spleen myeloid cells treated with LPS, similarly to humans and mice. Rat mir-155 is annotated only on the alternate genome, suggesting the presence of other "hidden" miRNAs on this assembly. Therefore, we comprehensively extended the homology search also to mice and humans, finally validating 34 novel mammalian miRNAs (two in humans, five in mice, and up to 27 in rats). Surprisingly, 15 of these novel miRNAs (one for mice and 14 for rats) were found only on the alternate and not on the reference genomic assembly. To date, our findings indicate that the choice of genomic assembly, when mapping small RNA reads, is an important option that should be carefully considered, at least for these animal models. Finally, the discovery of these novel mammalian miRNA genes may contribute to a better understanding of already acquired experimental data, thereby paving the way to still unexplored investigations and to unraveling the function of miRNAs in disease models.

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“…A base-pairing complement between the seed sequence of miRNAs and the 39 untranslated region (39UTR) of their target mRNAs is the key determinant of miRNA-target recognition. It is estimated that ,500-1000 miRNAs are expressed from the mammalian genome (Kiezun et al, 2012), many of which participate in regulation of a large variety of cellular processes including proliferation, differentiation and cell death (Inui et al, 2010;Chitwood and Timmermans, 2010). Furthermore, the majority of miRNAs show tissue or developmental stage-specific expression, suggesting an intricate role in these pathways (Chitwood and Timmermans, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…They are initially transcribed as large primary (pri) transcripts; these are then processed to precursor (pre) transcripts and then to the functional single-stranded mature miRNAs (Kiezun et al, 2012). A base-pairing complement between the seed sequence of miRNAs and the 39 untranslated region (39UTR) of their target mRNAs is the key determinant of miRNA-target recognition.…”

Section: Introductionmentioning

confidence: 99%

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

Ninio-Many

Grossman

Shomron

et al. 2013

Journal of Cell Science

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SummaryFyn, a member of the Src family kinases (SFKs), has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. MicroRNAs (miRNAs) play a major role in post-transcriptional repression of protein expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor-suppressing miRNA that is downregulated in several cancer cell types and on our bioinformatics studies presented here, we chose to examine the post-transcription regulation of Fyn by miR-125a-3p in the HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p. Following this reduction, the activity of proteins downstream of Fyn, such as FAK, paxillin and Akt (proteins known to be overexpressed in various tumors), is also reduced. On a broader level, we show that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration, probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p, as well as by the fact that numerous cancer cell lines show a significant downregulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, which implies that it has a therapeutic potential in overexpressed Fyn-related diseases.

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miRviewer: a multispecies microRNA homologous viewer

Cited by 72 publications

References 18 publications

Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines

Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines

Rat mir-155 generated from the lncRNA Bic is ‘hidden’ in the alternate genomic assembly and reveals the existence of novel mammalian miRNAs and clusters

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

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