Network analysis of microRNAs and their regulation in human ovarian cancer

Sebastian Schmeier, Ulf Schaefer, Magbubah Essack, Vladimir B. Bajic

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)183
JournalBMC Systems Biology
Volume5
Issue number1
DOIs
StatePublished - Nov 3 2011

ASJC Scopus subject areas

  • Structural Biology
  • Modeling and Simulation
  • Molecular Biology
  • Applied Mathematics

Fingerprint

Dive into the research topics of 'Network analysis of microRNAs and their regulation in human ovarian cancer'. Together they form a unique fingerprint.

Cite this