title: Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers.
abstract: Transcription factors (TFs) and microRNAs (miRNAs) form a gene regulatory network (GRN) at the transcriptional and post-transcriptional level in living cells. However, this network has not been well characterized, especially in regards to the mutual regulations between TFs and miRNAs in cancers. In this study, we collected those regulations inferred by ChIP-Seq or CLIP-Seq to construct the GRN formed by TFs, miRNAs, and target genes. To increase the reliability of the proposed network and examine the regulation activity of TFs and miRNAs, we further incorporated the mRNA and miRNA expression profiles in seven cancer types using The Cancer Genome Atlas data. We observed that regulation rewiring was prevalent during tumorigenesis and found that the rewired regulatory feedback loops formed by TFs and miRNAs were highly associated with cancer. Interestingly, we identified one regulatory feedback loop between STAT1 and miR-155-5p that is consistently activated in all seven cancer types with its function to regulate tumor-related biological processes. Our results provide insights on the losing equilibrium of the regulatory feedback loop between STAT1 and miR-155-5p influencing tumorigenesis.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Chen-Ching
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Ramkrishna
authors.initials: R
authors.lastname: Mitra
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Feixiong
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.|Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.|Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007157:Immunologic Surveillance / Q000235:genetics*; D056747:Immunomodulation; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex