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Computational analysis of biological functions and pathways collectively targeted by co-expressed microRNAs in cancer

Yuriy Gusev1, Thomas D Schmittgen, Megan Lerner

  • 1Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. yuriy-gusev@ouhsc.edu

BMC Bioinformatics
|December 6, 2007
PubMed
Abstract

Insights

Co-expressed microRNAs in cancer collectively target broad cellular functions and pathways, offering a compensatory response to abnormal cell changes. This systems biology approach aids in interpreting microRNA profiling data for cancer research.

Area of Science:

  • Computational biology
  • Genomics
  • Cancer research

Background:

  • Aberrant microRNAome expression is common in human cancers.
  • The global impact of co-expressed microRNAs on cellular functions in cancer is not fully understood.
  • Existing research has identified specific microRNA targets but lacks a comprehensive view of affected pathways.

Purpose of the Study:

  • To develop a computational method for analyzing biological processes and signaling pathways affected by co-expressed microRNAs in cancer.
  • To globally assess the collective impact of microRNAs on cancer cells.

Main Methods:

  • Computational analysis of five human cancer microRNA datasets.
  • Utilized the miRgate algorithm for combinatorial target prediction.
  • Employed a two-step data reduction to identify enriched Gene Ontology categories, biological functions, disease categories, toxicological categories, and signaling pathways.

Main Results:

  • Identified Gene Ontology categories, biological functions, disease categories, toxicological categories, and signaling pathways targeted by multiple microRNAs.
  • Found statistically significant enrichment of microRNA targets within these categories.
  • Confirmed that these targeted pathways are known to be affected in specific cancers.

Conclusions:

  • Co-expressed microRNAs collectively act as a systemic compensatory response to cancer-induced phenotypic changes.
  • MicroRNAs target a wide array of functional categories and signaling pathways relevant to specific cancers.
  • This systems biology approach offers novel interpretations of microRNA profiling data and generates testable hypotheses for microRNA's role in cancer.

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