title: Reconstruction and analysis of transcription factor-miRNA co-regulatory feed-forward loops in human cancers using filter-wrapper feature selection.
abstract: BACKGROUND
  As one of the most common types of co-regulatory motifs, feed-forward loops (FFLs) control many cell functions and play an important role in human cancers. Therefore, it is crucial to reconstruct and analyze cancer-related FFLs that are controlled by transcription factor (TF) and microRNA (miRNA) simultaneously, in order to find out how miRNAs and TFs cooperate with each other in cancer cells and how they contribute to carcinogenesis. Current FFL studies rely on predicted regulation information and therefore suffer the false positive issue in prediction results. More critically, FFLs generated by existing approaches cannot represent the dynamic and conditional regulation relationship under different experimental conditions.
  
  
  RESULTS
  In this study, we proposed a novel filter-wrapper feature selection method to accurately identify co-regulatory mechanism by incorporating prior information from predicted regulatory interactions with parallel miRNA/mRNA expression datasets. By applying this method, we reconstructed 208 and 110 TF-miRNA co-regulatory FFLs from human pan-cancer and prostate datasets, respectively. Further analysis of these cancer-related FFLs showed that the top-ranking TF STAT3 and miRNA hsa-let-7e are key regulators implicated in human cancers, which have regulated targets significantly enriched in cellular process regulations and signaling pathways that are involved in carcinogenesis.
  
  
  CONCLUSIONS
  In this study, we introduced an efficient computational approach to reconstruct co-regulatory FFLs by accurately identifying gene co-regulatory interactions. The strength of the proposed feature selection method lies in the fact it can precisely filter out false positives in predicted regulatory interactions by quantitatively modeling the complex co-regulation of target genes mediated by TFs and miRNAs simultaneously. Moreover, the proposed feature selection method can be generally applied to other gene regulation studies using parallel expression data with respect to different biological contexts.
authors.affiliation: School of Information Science and Technology, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Huanqing
authors.initials: H
authors.lastname: Feng
authors.forename: Ao
authors.initials: A
authors.lastname: Li
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C487931:mirnlet7 microRNA, human