Exploring novel key regulators in breast cancer network

PLoS One. 2018 Jun 21;13(6):e0198525. doi: 10.1371/journal.pone.0198525. eCollection 2018.

Abstract

The breast cancer network constructed from 70 experimentally verified genes is found to follow hierarchical scale free nature with heterogeneous modular organization and diverge leading hubs. The topological parameters (degree distributions, clustering co-efficient, connectivity and centralities) of this network obey fractal rules indicating absence of centrality lethality rule, and efficient communication among the components. From the network theoretical approach, we identified few key regulators out of large number of leading hubs, which are deeply rooted from top to down of the network, serve as backbone of the network, and possible target genes. However, p53, which is one of these key regulators, is found to be in low rank and keep itself at low profile but directly cross-talks with important genes BRCA2 and BRCA3. The popularity of these hubs gets changed in unpredictable way at various levels of organization thus showing disassortive nature. The local community paradigm approach in this network shows strong correlation of nodes in majority of modules/sub-modules (fast communication among nodes) and weak correlation of nodes only in few modules/sub-modules (slow communication among nodes) at various levels of network organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cluster Analysis
  • Female
  • Humans
  • Protein Interaction Maps / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Grants and funding

SA and MZM are financially supported by Indian Council of Medical Research under SRF (Senior Research Fellowship) and R.K.B.S by UPOE-II (UGC) (101), New Delhi, India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.