OligoHeatMap (OHM): an online tool to estimate and display hybridizations of oligonucleotides onto DNA sequences

Croce, Olivier; Chevenet, François; Christen, Richard

doi:10.1093/nar/gkn221

Cited by 102 publications

(97 citation statements)

References 13 publications

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“…In the next step, predicted interactions between miRNAs and target genes were considered, as they provide a useful subset of linked miRNA and mRNA data. There are numerous resources of experimentally validated or computationally predicted interactions between miRNAs and target mRNAs, such as TarBase [31], miranda [32], miRBase [17], MirTarget2 [33] and TargetScan [18]. Access to these databases is provided by the R package RmiR.Hs.miRNA, which provides the possibility to download the data in form of interaction tables.…”

Section: Resultsmentioning

confidence: 99%

“…Silencing of gene expression by such post-transcriptional processes has been identified as a new level of gene regulation which is capable of modulating expression levels. In the human genome, more than two thousand mature miRNAs have been identified [17]. Much effort has been put into the revelation of the complex functional network of miRNA and target gene regulation.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation

Weber

Sotoca

Kupfer

et al. 2013

BMC Systems Biology

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BackgroundNetwork inference from gene expression data is a typical approach to reconstruct gene regulatory networks. During chondrogenic differentiation of human mesenchymal stem cells (hMSCs), a complex transcriptional network is active and regulates the temporal differentiation progress. As modulators of transcriptional regulation, microRNAs (miRNAs) play a critical role in stem cell differentiation. Integrated network inference aimes at determining interrelations between miRNAs and mRNAs on the basis of expression data as well as miRNA target predictions. We applied the NetGenerator tool in order to infer an integrated gene regulatory network.ResultsTime series experiments were performed to measure mRNA and miRNA abundances of TGF-beta1+BMP2 stimulated hMSCs. Network nodes were identified by analysing temporal expression changes, miRNA target gene predictions, time series correlation and literature knowledge. Network inference was performed using NetGenerator to reconstruct a dynamical regulatory model based on the measured data and prior knowledge. The resulting model is robust against noise and shows an optimal trade-off between fitting precision and inclusion of prior knowledge. It predicts the influence of miRNAs on the expression of chondrogenic marker genes and therefore proposes novel regulatory relations in differentiation control. By analysing the inferred network, we identified a previously unknown regulatory effect of miR-524-5p on the expression of the transcription factor SOX9 and the chondrogenic marker genes COL2A1, ACAN and COL10A1.ConclusionsGenome-wide exploration of miRNA-mRNA regulatory relationships is a reasonable approach to identify miRNAs which have so far not been associated with the investigated differentiation process. The NetGenerator tool is able to identify valid gene regulatory networks on the basis of miRNA and mRNA time series data.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation

Weber

Sotoca

Kupfer

et al. 2013

BMC Systems Biology

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“…Three bioinformatic databases were used for the in silico prediction of miR-155 targets: TargetScan [58], microRNA.org [59,60] and MicroCosm [61]. Predicted target genes were obtained that were common to at least 2 of the 3 databases or 3 of the 3 databases (accessed on 27/7/2012).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-155 as an inducer of apoptosis and cell differentiation in Acute Myeloid Leukaemia

et al. 2014

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BackgroundAcute myeloid leukaemia (AML) is characterised by the halt in maturation of myeloid progenitor cells, combined with uncontrolled proliferation and abnormal survival, leading to the accumulation of immature blasts. In many subtypes of AML the underlying causative genetic insults are not fully described. MicroRNAs are known to be dysregulated during oncogenesis. Overexpression of miR-155 is associated with some cancers, including haematological malignancies, and it has been postulated that miR-155 has an oncogenic role. This study investigated the effects of modulating miR-155 expression in human AML cells, and its mechanism of action.ResultsAnalysis of miR-155 expression patterns in AML patients found that Fms-like tyrosine kinase 3 (FLT3)-wildtype AML has the same expression level as normal bone marrow, with increased expression restricted to AML with the FLT3-ITD mutation. Induction of apoptosis by cytarabine arabinoside or myelomonocytic differentiation by 1,23-dihydroxyvitaminD3 in FLT3-wildtype AML cells led to upregulated miR-155 expression. Knockdown of miR-155 by locked nucleic acid antisense oligonucleotides in the FLT3-wildtype AML cells conferred resistance to cytarabine arabinoside induced apoptosis and suppressed the ability of cells to differentiate.Ectopic expression of miR-155 in FLT3-wildtype AML cells led to a significant gain of myelomonocytic markers (CD11b, CD14 and CD15), increase in apoptosis (AnnexinV binding), decrease in cell growth and clonogenic capacity.In silico target prediction identified a number of putative miR-155 target genes, and the expression changes of key transcription regulators of myeloid differentiation and apoptosis (MEIS1, GF1, cMYC, JARID2, cJUN, FOS, CTNNB1 and TRIB2) were confirmed by PCR. Assessment of expression of apoptosis-related proteins demonstrated a marked increase in cleaved caspase-3 expression confirming activation of the apoptosis cascade.ConclusionsThis study provides evidence for an anti-leukaemic role for miR-155 in human FLT3-wildtype AML, by inducing cell apoptosis and myelomonocytic differentiation, which is in contrast to its previously hypothesized role as an oncogene. This highlights the complexity of gene regulation by microRNAs that may have tumour repressor or oncogenic effects depending on disease context or tissue type.

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“…Until now, thousands of miRNAs have been reported in animals, plants and viruses (miRBase: http://www.mirbase.org) [16]. Many miRNAs are highly conserved across divergent species while others are specific to a particular evolutionary lineage [13,15].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of the expression profile of microRNAs in Anopheles anthropophagus

et al. 2014

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BackgroundAnopheles anthropophagus, one of the most important mosquito-borne disease vectors in Asia, mainly takes blood meals from humans and transmits both malaria and filariae. MicroRNAs (miRNAs) are small non-coding RNAs, and play a critical role in many cellular processes, including development, differentiation, apoptosis and innate immunity.MethodsWe investigated the global miRNA expression profile of male and female adults of A. anthropophagus using illumina Hiseq2000 sequencing combined with Northern blot.ResultsBy using the miRNAs of the closely-related species Anopheles gambiae and Aedes aegypti as reference, we obtained 102 miRNAs candidates out of 12.43 million raw sequencing reads for male and 16.51 million reads for female, with 81 of them found as known miRNAs in An. gambiae and/or Ae. aegypti, and the remaining 21 miRNAs were considered as novel. By analyzing the revised read count of miRNAs in male and female, 29 known miRNAs show sexual difference expression: >2-fold in the read count of the same miRNAs in male and female. Especially for miR-989, which is highly expressed in the female mosquitoes, but shows almost no detected expression in male mosquitoes, indicating that miR-989 may be involved in the physiological activity of female mosquito adults. The expression of four miRNAs in different growth stages of mosquito were further identified by Northern blot. Several miRNAs show the stage-specific expression, of which miR-2943 only expressed in the egg stage, suggesting that miR-2943 may be associated with the development of mosquito eggs.ConclusionsThe present study represents the first global characterization of An. anthropophagus miRNAs in sexual differences and stage-specific functions. A better understanding of the functions of these miRNAs will offer new insights in mosquito biology and has implications for the effective control of mosquito-borne infectious diseases.

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OligoHeatMap (OHM): an online tool to estimate and display hybridizations of oligonucleotides onto DNA sequences

Cited by 102 publications

References 13 publications

Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation

Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation

MicroRNA-155 as an inducer of apoptosis and cell differentiation in Acute Myeloid Leukaemia

Identification and characterization of the expression profile of microRNAs in Anopheles anthropophagus

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