Inferring miRNA sponge co-regulation of protein-protein interactions in human breast cancer

Junpeng Zhang1, Thuc Duy Le2,3, Lin Liu2

  • 1School of Engineering, Dali University, Dali, Yunnan, 671003, People's Republic of China. zhangjunpeng_411@yahoo.com.

BMC Bioinformatics
|May 10, 2017
PubMed
Abstract

Insights

We developed miRSCoPPI to uncover how microRNA (miRNA) sponges co-regulate protein-protein interactions (PPIs) in breast cancer. This method identifies key biological pathways and potential prognostic markers, offering new insights into cancer development.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • MicroRNA (miRNA) sponges are increasingly recognized for their role in cancer.
  • The co-regulatory functions of miRNA sponges in protein-protein interactions (PPIs) remain largely unexplored.
  • Understanding these interactions is crucial for advancing cancer research.

Purpose of the Study:

  • To develop a novel computational method, miRSCoPPI, for inferring miRNA sponge co-regulation of PPIs.
  • To investigate these co-regulatory networks specifically within the context of breast cancer (BRCA).
  • To identify potential biomarkers and therapeutic targets through network analysis.

Main Methods:

  • Integrated heterogeneous data: miRNA, long non-coding RNA (lncRNA), messenger RNA (mRNA) expression, miRNA-target, PPI, and lncRNA-target interactions.
  • Developed a multi-step inference method (miRSCoPPI) to model miRNA sponge co-regulation of PPIs.
  • Applied graph clustering and pathway enrichment analysis to identify significant modules and biological pathways.

Main Results:

  • The inferred breast cancer-related miRSCoPPI network is highly connected and scale-free.
  • Identified 17 significant BRCA-related miRSCoPPI modules, with several enriched in cancer-associated pathways.
  • Ten modules demonstrated strong performance in classifying tumor versus normal samples, serving as potential prognostic signatures.
  • The method showed robustness using both experimentally validated and computationally predicted miRNA-target interactions.

Conclusions:

  • miRSCoPPI is an effective tool for inferring miRNA sponge co-regulation of PPIs in breast cancer.
  • The findings provide valuable insights into the complex regulatory roles of miRNA sponges in cancer.
  • This approach can facilitate the discovery of novel biomarkers and therapeutic strategies for breast cancer.

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