Systematic dissection of dysregulated transcription factor-miRNA feed-forward loops across tumor types

Briefings in Bioinformatics
|December 15, 2015
PubMed

Insights

This study identifies 26 cross-cancer feed-forward loops (FFLs) dysregulated in multiple tumor types. These pan-cancer FFLs offer insights into cancer mechanisms and potential new drug targets.

Area of Science:

  • Genomics
  • Systems Biology
  • Cancer Research

Background:

  • Transcription factors and microRNAs (miRNAs) form feed-forward loops (FFLs) that mutually regulate each other and target genes.
  • Dysregulated FFLs are implicated in various cancers, but a pan-cancer perspective is lacking.

Purpose of the Study:

  • To systematically identify and analyze dysregulated feed-forward loops across multiple cancer types (pan-cancer FFLs).
  • To explore the functional relationships and therapeutic potential of these pan-cancer FFLs.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) data for comprehensive analysis.
  • Identified 26 pan-cancer FFLs dysregulated in at least five tumor types.
  • Analyzed network properties, functional subnetworks, and enrichment of cancer-associated genes and drug targets.

Main Results:

  • Discovered 26 pan-cancer FFLs with significant dysregulation across multiple cancers.
  • These FFLs form interconnected subnetworks, including those related to epithelial-to-mesenchymal transition.
  • Identified enrichment of cancer genes, drug targets, and network hubs/bottlenecks within these FFLs.
  • Found that proteins and miRNAs within subnetworks often belong to the same families.

Conclusions:

  • Pan-cancer FFLs represent a conserved regulatory mechanism across diverse tumor types.
  • These FFLs provide a novel framework for understanding cancer pathogenesis.
  • The identified FFLs and associated genes/miRNAs are promising targets for novel anticancer drug development.

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