title: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Ramkrishna
authors.initials: R
authors.lastname: Mitra
authors.forename: Chen-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Feixiong
authors.initials: F
authors.lastname: Cheng
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D058750:Epithelial-Mesenchymal Transition; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs; D009369:Neoplasms; D014157:Transcription Factors
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors
keywords:  drug repositioning; TF and miRNA regulatory network; feed-forward loop; gene and miRNA expression; pan-cancer