title: Revealing potential molecular targets bridging colitis and colorectal cancer based on multidimensional integration strategy.
abstract: Chronic inflammation may play a vital role in the pathogenesis of inflammation-associated tumors. However, the underlying mechanisms bridging ulcerative colitis (UC) and colorectal cancer (CRC) remain unclear. Here, we integrated multidimensional interaction resources, including gene expression profiling, protein-protein interactions (PPIs), transcriptional and post-transcriptional regulation data, and virus-host interactions, to tentatively explore potential molecular targets that functionally link UC and CRC at a systematic level. In this work, by deciphering the overlapping genes, crosstalking genes and pivotal regulators of both UC- and CRC-associated functional module pairs, we revealed a variety of genes (including FOS and DUSP1, etc.), transcription factors (including SMAD3 and ETS1, etc.) and miRNAs (including miR-155 and miR-196b, etc.) that may have the potential to complete the connections between UC and CRC. Interestingly, further analyses of the virus-host interaction network demonstrated that several virus proteins (including EBNA-LP of EBV and protein E7 of HPV) frequently inter-connected to UC- and CRC-associated module pairs with their validated targets significantly enriched in both modules of the host. Together, our results suggested that multidimensional integration strategy provides a novel approach to discover potential molecular targets that bridge the connections between UC and CRC, which could also be extensively applied to studies on other inflammation-related cancers.
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guan
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yi
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xishan
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Guiyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.|Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003092:Colitis / Q000150:complications / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology*; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D060066:Protein Interaction Maps
chemical_list: D015415:Biomarkers
keywords: colitis; colorectal cancer; crosstalk; network analysis; pivot