Genome-wide survey of microRNA–transcription factor feed-forward regulatory circuits in human

Re, Angela; Corà, Davide; Taverna, Daniela; Caselle, Michele

doi:10.1039/b900177h

Cited by 103 publications

(104 citation statements)

References 53 publications

(188 reference statements)

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“…Genome-scale analyses revealed that feedback and feedforward loops that contain miRNAs are also recurrent network motifs in large gene networks (Tsang et al, 2007;Martinez et al, 2008;Re et al, 2009), so that miRNAs can provide biological robustness by participating in these loops (Hornstein and Shomron, 2006;Wu et al, 2009a;Herranz and Cohen, 2010;Osella et al, 2011;Pelaez and Carthew, 2012). miRNAs are small (approximately 22 nucleotides) noncoding single-stranded RNAs that regulate gene expression post-transcriptionally.…”

Section: Mirna-containing Circuits Contribute To the Robustness Of Bimentioning

confidence: 99%

Robustness of the hypoxic response: Another job for miRNAs?

Ezcurra

Bertolin

Melani

et al. 2012

Developmental Dynamics

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Living organisms are constantly exposed to environmental and genetic perturbations. Biological robustness enables these organisms to maintain their functional stability in the presence of external or internal changes. It has been proposed that microRNAs (miRNAs), small non-coding regulatory RNAs, contribute to robustness of gene regulatory networks. The hypoxic response is a major and well-characterized example of a cellular and systemic response to environmental stress that needs to be robust. miRNAs regulate the response to hypoxia, both at the level of the main transcription factor that mediates this response, the hypoxia-inducible factor (HIF), and at the level of one of the most important systemic outcomes of the response: angiogenesis. In this review, we will take the hypoxic response as a paradigm of miRNAs participating in circuits that provide robustness to biological responses.

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Section: Mirna-containing Circuits Contribute To the Robustness Of Bimentioning

confidence: 99%

Robustness of the hypoxic response: Another job for miRNAs?

Ezcurra

Bertolin

Melani

et al. 2012

Developmental Dynamics

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“…Recently several studies have shown that the transcriptional regulation by transcription factors (TFs) and posttranscriptional regulation by miRNAs are often highly coordinated (Shimoni et al 2007;Tsang et al 2007;Shalgi et al 2007;Re et al 2009;Martinez et al 2008;Martinez and Walhout 2009;Yu et al 2008;Inui et al 2010;Ivey and Srivastava 2010). Of particular relevance is the accumulating evidence that the interplay of miRNAs and transcriptional regulators such as activators and repressors regulates key developmental events and cell fate decisions (Johnston et al 2005;Kim 2007;Fazi 2005;Juan et al 2009;Bracken 2008;Li and Carthew 2005;Visvanathan et al 2007;Xu et al 2009;Zhao et al 2009;Pospisil 2011).…”

Section: Introductionmentioning

confidence: 99%

“…The regulatory roles of miRNAs have been a subject of research for the last several years, both experimentally and theoretically (Shimoni et al 2007;Wang and Raghavachari 2011;Levine et al 2007; Levine and Hwa 2008;Mehta et al 2008;Osella et al 2011;Mitarai et al 2009;Bumgarner et al 2009;Iliopoulos et al 2009). Although some of the miRNAs have been well studied, the mechanisms of various functions and biological significance of miRNAs are still not well understood (Bumgarner et al 2009;Iliopoulos et al 2009;Tsang et al 2007;Shalgi et al 2007;Re et al 2009;Martinez et al 2008;Martinez and Walhout 2009;Yu et al 2008;Inui et al 2010;Ivey and Srivastava 2010;Johnston et al 2005;Kim 2007;Fazi 2005;Juan et al 2009;Bracken 2008;Li and Carthew 2005;Visvanathan et al 2007;Xu et al 2009;Zhao et al 2009;Pospisil 2011).…”

Section: Introductionmentioning

confidence: 99%

Functional characteristics of a double negative feedback loop mediated by microRNAs

2013

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MicroRNAs (miRNAs) are a class of small, noncoding RNAs that play crucial roles in almost all cellular processes. As key post-transcriptional regulators of gene expression, miRNAs mainly induce mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance of motifs involving miRNAs and transcriptional factors (TFs). Here, we study the functional characteristics of one such motif, a two-node miRNA-mediated double negative feedback loop (MDNFL) in which a TF suppresses an miRNA and the TF itself is negatively regulated by the miRNA. Several examples of this motif are described from the literature. We propose a general computational model for the MDNFL based on biochemical regulations and explore its dynamics by using bifurcation analysis. Our results show that the MDNFL can behave as a bistable switch. This functional feature is in agreement with experimental observations of the widespread appearance of miRNAs in fate decisions such as differentiation during development. Importantly, it is found that under the interplay of a TF and an miRNA, the MDNFL model can behave as switches for wide ranges of parameters even without cooperative binding of the TF. In addition, we also investigate how extrinsic noise affects dynamic behavior of the MDNFL. Interestingly, it is found that when the MDNFL is in the bistable region, by choosing the appropriate extrinsic noise source, the MDNFL system can switch from one steady state to the other and meanwhile the production of either miRNA or protein is amplified significantly. From an engineering perspective, this noisebased switch and amplifier for gene expression is very easy to control. It is hoped that the results presented here would provide a new insight on how gene expression is regulated by miRNAs and further guidance for experiments.

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“…The mechanisms and consequences of miR deregulation within a cancer cell are still being determined, although it is likely that changes in the levels and the activity of transcriptional regulators and the miR-processing machinery, coupled with alterations in miR copy number, contribute to the overall deregulation of miR expression (Zhang et al, 2006;Selcuklu et al, 2009). There is now evidence for the participation of miR and transcription factor combinations in feedback and feed-forward loops (Tsang et al, 2007;Brosh et al, 2008;Bartel, 2009;Re et al, 2009), and such miR/transcription factor feed-forward loops enhance the robustness and responsiveness of the gene regulation network (Filipowicz et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells

et al. 2011

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The transcription factor FOXP3 has been identified as a tumour suppressor in the breast and prostate epithelia, but little is known about its specific mechanism of action. We have identified a feed-forward regulatory loop in which FOXP3 suppresses the expression of the oncogene SATB1.In particular, we demonstrate that SATB1 is not only a direct target of FOXP3 repression, but that FOXP3 also induces two miRs, miR-7 and miR-155, which specifically target the 3 0 -UTR of SATB1 to further regulate its expression. We conclude that FOXP3-regulated miRs form part of the mechanism by which FOXP3 prevents the transformation of the healthy breast epithelium to a cancerous phenotype. Approaches aimed at restoring FOXP3 function and the miRs it regulates could help provide new approaches to target breast cancer.

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Genome-wide survey of microRNA–transcription factor feed-forward regulatory circuits in human

Abstract: In this work, we describe a computational framework for the genome-wide identification and characterization of mixed transcriptional/post-transcriptional regulatory circuits in humans.

Cited by 103 publications

References 53 publications

Robustness of the hypoxic response: Another job for miRNAs?

Robustness of the hypoxic response: Another job for miRNAs?

Functional characteristics of a double negative feedback loop mediated by microRNAs

FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells

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