Network analysis of microRNAs and their regulation in human ovarian cancer

Handle URI:
http://hdl.handle.net/10754/325267
Title:
Network analysis of microRNAs and their regulation in human ovarian cancer
Authors:
Schmeier, Sebastian; Schaefer, Ulf; Essack, Magbubah ( 0000-0003-2709-5356 ) ; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
Abstract:
Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our understanding of the molecular mechanisms underlying human cancer development and OC in particular. 2011 Schmeier et al; licensee BioMed Central Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Schmeier S, Schaefer U, Essack M, Bajic VB (2011) Network analysis of microRNAs and their regulation in human ovarian cancer. BMC Systems Biology 5: 183. doi:10.1186/1752-0509-5-183.
Publisher:
Springer Nature
Journal:
BMC Systems Biology
Issue Date:
3-Nov-2011
DOI:
10.1186/1752-0509-5-183
PubMed ID:
22050994
PubMed Central ID:
PMC3219655
Type:
Article
ISSN:
17520509
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchmeier, Sebastianen
dc.contributor.authorSchaefer, Ulfen
dc.contributor.authorEssack, Magbubahen
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-08-27T09:43:43Z-
dc.date.available2014-08-27T09:43:43Z-
dc.date.issued2011-11-03en
dc.identifier.citationSchmeier S, Schaefer U, Essack M, Bajic VB (2011) Network analysis of microRNAs and their regulation in human ovarian cancer. BMC Systems Biology 5: 183. doi:10.1186/1752-0509-5-183.en
dc.identifier.issn17520509en
dc.identifier.pmid22050994en
dc.identifier.doi10.1186/1752-0509-5-183en
dc.identifier.urihttp://hdl.handle.net/10754/325267en
dc.description.abstractBackground: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our understanding of the molecular mechanisms underlying human cancer development and OC in particular. 2011 Schmeier et al; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectmicroRNAen
dc.subjecttranscription factoren
dc.subjectapoptosisen
dc.subjectbinding siteen
dc.subjectcell cycleen
dc.subjectgene expression regulationen
dc.subjectgeneticsen
dc.subjectmetabolismen
dc.subjectovary tumoren
dc.subjectphysiologyen
dc.subjectprotein protein interactionen
dc.subjectApoptosisen
dc.subjectBinding Sitesen
dc.subjectCell Cycleen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectMicroRNAsen
dc.subjectOvarian Neoplasmsen
dc.subjectProtein Interaction Mapsen
dc.subjectTranscription Factorsen
dc.titleNetwork analysis of microRNAs and their regulation in human ovarian canceren
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalBMC Systems Biologyen
dc.identifier.pmcidPMC3219655en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionUnidad Académica de Sistemas Arrecifales (Puerto Morelos), Instituto de Ciencias Del Mar y Limnología, Universidad Nacional Autõnoma de México, Puerto Morelos, QR 77580, Mexicoen
dc.contributor.institutionSchool of Natural Sciences, University of California Merced, 5200 North Lake Road, Merced, CA 95343, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorSchmeier, Sebastianen
kaust.authorEssack, Magbubahen
kaust.authorBajic, Vladimir B.en
kaust.authorSchaefer, Ulfen
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