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Updated: Mar 29, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Systematic dissection of dysregulated transcription factor-miRNA feed-forward loops across tumor types
Abstract:
Transcription factor and microRNA (miRNA) can mutually regulate each other and jointly regulate their shared target genes to form feed-forward loops (FFLs). While there are many studies of dysregulated FFLs in a specific cancer, a systematic investigation of dysregulated FFLs across multiple tumor types (pan-cancer FFLs) has not been performed yet. In this study, using The Cancer Genome Atlas data, we identified 26 pan-cancer FFLs, which were dysregulated in at least five tumor types. These pan-cancer FFLs could communicate with each other and form functionally consistent subnetworks, such as epithelial to mesenchymal transition-related subnetwork. Many proteins and miRNAs in each subnetwork belong to the same protein and miRNA family, respectively. Importantly, cancer-associated genes and drug targets were enriched in these pan-cancer FFLs, in which the genes and miRNAs also tended to be hubs and bottlenecks. Finally, we identified potential anticancer indications for existing drugs with novel mechanism of action. Collectively, this study highlights the potential of pan-cancer FFLs as a novel paradigm in elucidating pathogenesis of cancer and developing anticancer drugs.
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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