miRIAD—integrating microRNA inter- and intragenic data

Hinske, Christian; França, Gustavo S.; Torres, Hugo A. M.; O’Hara, Daniel T.; Lopes‐Ramos, Camila M.; Heyn, Jens; Reis, Luiz F. L.; Ohno-Machado, Lucila; Kreth, Simone; Galante, Pedro A. F.

doi:10.1093/database/bau099

Cited by 91 publications

(92 citation statements)

References 30 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of miRNA location and putative ER binding sites in the regulatory region of the miRNA precursors miRIAD software, a web search tool designed to obtain integrated information about intragenic miRNA and their host genes, was used to know E2-induced miRNA location [23]. Moreover, in silico analysis of ER putative binding sites within the regulatory region of miRNA was performed by using available online bioinformatic tools.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNAgene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.

show abstract

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Some miRNAs are located within genomic regions of protein-coding genes or noncoding genes (Rodriguez et al 2004;Hinske et al 2010Hinske et al , 2014. These intragenic miRNAs were studied with their host genes and the results suggest that a complex transcription and regulation relationship exists between them (Monteys et al 2010;Yan et al 2011;Son et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…However, some animal miRNAs are discovered as transcribed antisense to exons of noncoding or protein-coding genes (Bartel 2004). Such antisense exonic miRNAs, together with the intronic miRNAs and the miRNAs in the sense strand of genes, are termed as intragenic miRNAs (Rodriguez et al 2004;Hinske et al 2010Hinske et al , 2014. The function of such antisense exonic miRNAs were investigated in mouse miR-126 and miR-136 that are transcribed antisense of a retrotransposon-like gene (RTL1) and a down-regulated RTL1 mRNA level through a fully complementary sequence match with the target gene (Seitz et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Systematic study of cis-antisense miRNAs in animal species reveals miR-3661 to target PPP2CA in human cells

Wang

Li²,

Liu

et al. 2015

RNA

View full text Add to dashboard Cite

MicroRNAs (miRNAs) suppress targeting gene expression through blocking translation or triggering mRNA degradation and, in general, act in trans, through a partially complementary interaction with the 3 ′ untranslated region (3 ′ UTR) or coding regions of a target gene. Although it has been reported previously that some miRNAs suppress their target genes on the opposite strand with a fully complementary sequence (i.e., natural antisense miRNAs that act in cis), there is no report to systematically study such cis-antisense miRNAs in different animal species. Here we report that cis-antisense miRNAs do exist in different animal species: 48 in Caenorhabditis elegans, 17 in Drosophila, 36 in Mus musculus, and 52 in Homo sapiens using a systematical bioinformatics approach. We show that most of these cis-antisense miRNAs can efficiently reduce the expression levels of their target genes in human cells. We further investigate hsa-miR-3661, one of the predicted cis-antisense miRNAs, in detail and demonstrate that this miRNA directly targets the coding sequence of PPP2CA located on the opposite DNA strand and inhibits the PPP2CA expression. Taken together, these results indicate that cis-antisense miRNAs are conservative and functional in animal species including humans.

show abstract

“…MiRNA classification into intergenic and intragenic was downloaded from the miRIAD database version 2014 (Hinske et al, 2014).…”

Section: Data Setsmentioning

confidence: 99%

A statistical model for epigenetic control of miRNAs

Sousa

Marsico

2016

Preprint

View full text Add to dashboard Cite

ABSTRACTmicroRNAs are small, non-coding RNAs involved in post-transcriptional gene regulation. Since the dysregulation of only a few miRNAs can affect many biological pathways, miRNAs are thought to play a key role in cancer development and can be used as biomarkers for cancer diagnosis and prognosis. In order to understand how miRNA dysregulation leads to a cancer phenotype it is important to determine the basic regulatory mechanisms that drive miRNA expression. Although much is known about miRNA-mediated post-transcriptional regulation, little is known about the epigenetic control of miRNAs. Here, we performed cell-line specific miRNA promoter predictions and built a classification model for expressed and non-expressed miRNAs based on several epigenetic features, e.g. histone marks and DNA methylation at both, miRNA promoters and around miRNA hairpins. We were able to classify intragenic and intergenic miRNAs with an accuracy of 79% and 85%, respectively, and identified the most important features for classification via feature selection. Surprisingly, we found that DNA methylation seems to have a dual role in regulating miRNA expression at transcriptional level: at promoters, high levels of DNA methylation correlate with transcriptional repression, while around miRNA hairpins high levels of DNA methylation have a positive impact on the expression level of the mature miRNA.

show abstract

miRIAD—integrating microRNA inter- and intragenic data

Cited by 91 publications

References 30 publications

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Systematic study of cis-antisense miRNAs in animal species reveals miR-3661 to target PPP2CA in human cells

A statistical model for epigenetic control of miRNAs

Contact Info

Product

Resources

About