miR2Gene: pattern discovery of single gene, multiple genes, and pathways by enrichment analysis of their microRNA regulators

Qiu, Chengxiang; Wang, Juan; Cui, Qinghua

doi:10.1186/1752-0509-5-s2-s9

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…It is well known that single miRNA molecule might regulate multiple genes simultaneously ( Qiu et al, 2011 ) thereby regulating multiple pathways. In order to investigate which biological pathways are affected by let-7 miRNA, we applied miRPath v.3, a miRNA pathway analysis tool.…”

Section: Resultsmentioning

confidence: 99%

Modulation of Alpha-synuclein Expression and Associated Effects by MicroRNA Let-7 in Transgenic C. elegans

Shamsuzzama

Kumar

Nazir

2017

Front. Mol. Neurosci.

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Neurodegenerative Parkinson’s disease (PD) is a multi-factorial disorder lacking complete cure. Understanding the complete mechanism of initiation and progression of this disease has been quite challenging; however, progress has been made toward deciphering certain genetic aspects related to the disease condition. Genetics studies have provided clues toward the role of microRNAs (miRNAs) in various disease conditions. One of the crucial miRNA molecules, let-7, is highly conserved miRNA and is known to regulate important functions of development and viability; its altered expression has been reported in C. elegans model of PD. We carried out studies with let-7, employing transgenic C. elegans model expressing ‘human’ alpha-synuclein and developed a let-7 loss-of-function model toward studying the downstream effects related to PD. We observed that let-7 miRNA was upregulated in C. elegans model of PD and figured that loss of let-7 miRNA leads to decreased alpha-synuclein expression, increased autophagy, increased Daf-16 expression, increased oxidative stress and increased lipid content with no effect on dopaminergic/acetylcholinergic neurons. Our findings indicate that let-7 miRNA regulates PD-associated pathways. Our study provides insight toward the role of let-7 in regulating expression of genes associated with these pathways which might have implications on the multi-factorial nature of PD. Potential pharmacological agents modulating the expression of let-7 could be studied toward targeting the multi-factorial aspect of PD.

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Section: Resultsmentioning

confidence: 99%

Modulation of Alpha-synuclein Expression and Associated Effects by MicroRNA Let-7 in Transgenic C. elegans

Shamsuzzama

Kumar

Nazir

2017

Front. Mol. Neurosci.

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“…Fifteen different web-based bioinformatics algorithms (DIANA-microT-CDS, DIANA-microT, MicroCosm, miR2Gene, miRanda-MirSVR, miRBRIDGE, miRSystem, miRTar, PACCMIT, PicTar, PITA, RegRNA, RNA22, TargetScan, and TargetSpy) that were freely-available online were used to predict microRNA targeting (John et al, 2004 ; Krek et al, 2005 ; Griffiths-Jones et al, 2006 ; Huang et al, 2006 ; Miranda et al, 2006 ; Kertesz et al, 2007 ; Sturm et al, 2010 ; Tsang et al, 2010 ; Hsu et al, 2011 ; Qiu et al, 2011 ; Lu et al, 2012 ; Vlachos et al, 2012 ) (Supplementary Table S1). These bioinformatics algorithms were selected to predict microRNA targeting based on a number of different features including; sequence complementarity, target site accessibility, binding energy, and conservation of target sites in order to increase precision and power.…”

Section: Methodsmentioning

confidence: 99%

Genetic variation in the 3â€²-UTR of CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7: potential effects on regulation by microRNA and pharmacogenomics relevance

Swart

Dandara

2014

Front. Genet.

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Introduction: Pharmacogenomics research has concentrated on variation in genes coding for drug metabolizing enzymes, transporters and nuclear receptors. However, variation affecting microRNA could also play a role in drug response. This project set out to investigate potential microRNA target sites in 11 genes and the extent of variation in the 3′-UTR of six selected genes; CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7.Methods: Fifteen microRNA target prediction algorithms were used to identify microRNAs predicted to regulate 11 genes. The 3′-UTR of the 6 genes which topped the list of potential microRNA targets was sequenced in 30 black South Africans. In addition, genetic variants within these genes were investigated for interference with mRNA-microRNA interactions. Potential effects of observed variants were determined using in silico prediction tools.Results: The 11 genes coding for DMEs, transporters and nuclear receptors were predicted to be targets of microRNAs with CYP2B6, NR1I2 (PXR), CYP3A4, and CYP1A2, interacting with the most microRNAs. The majority of identified genetic variants were predicted to interfere with microRNA regulation. For example, the variant, rs1054190C in NR1I2 was predicted to result in the presence of a binding site for the microRNA miR-1250-5p, while the variant rs1054191G was predicted to result in the absence of a recognition site for miR-371b-3p, miR-4258 and miR-4707-3p. Fifteen of the seventeen, novel variants occurred within microRNA target sequences.Conclusion: The 3′-UTR harbors variation that is likely to influence regulation of specific genes by microRNA. In silico prediction followed by functional validation could aid in decoding the contribution of variation in the 3′-UTR, to some unexplained heritability that affects drug response. Understanding the specific role of each microRNA may lead to identification of markers for targeted therapy and therefore improve personalized drug treatment.

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“…Another comprehensive analysis established a dictionary on miRNAs and their putative target pathways and uncovered that differentially expressed genes in cancers were enriched with targets of certain miRNAs [ 10 ]. Qiu et al developed a miR2Gene tool to discover the pattern of gene and pathways by enrichment analysis of their miRNA regulators [ 11 ]. Recent studies performed an integrated analysis of miRNA and gene expression profiles to miRNA-gene regulatory network in complex diseases [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3

Huang

et al. 2016

Oncotarget

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MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher's exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo.life.hust.edu.cn/miR_path). As one of the miRNAs targeting many cancer related pathways, miR-142-5p potentially regulates the maximum number of genes in TGF-β signaling pathway. We experimentally confirmed that miR-142-5p directly targeted and suppressed SMAD3, a key component in TGF-β signaling. Ectopic overexpression of miR-142-5p significantly promoted tumor cell proliferation and inhibited apoptosis, while silencing of miR-142-5p inhibited the tumor cell proliferation and promoted apoptosis in vitro. These findings indicate that miR-142-5p plays as a negative regulator in TGF-β pathway by targeting SMAD3 and suppresses TGF-β-induced growth inhibition in cancer cells. Our study proved the feasibility of miRNA regulatory pathway analysis and shed light on combining bioinformatics with experiments in the research of complex diseases.

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miR2Gene: pattern discovery of single gene, multiple genes, and pathways by enrichment analysis of their microRNA regulators

Cited by 9 publications

References 21 publications

Modulation of Alpha-synuclein Expression and Associated Effects by MicroRNA Let-7 in Transgenic C. elegans

Modulation of Alpha-synuclein Expression and Associated Effects by MicroRNA Let-7 in Transgenic C. elegans

Genetic variation in the 3â€²-UTR of CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7: potential effects on regulation by microRNA and pharmacogenomics relevance

MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3

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