Revealing potential molecular targets bridging colitis and colorectal cancer based on multidimensional integration strategy
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Xu Guan1,*, Ying Yi2,*, Yan Huang2,*, Yongfei Hu2, Xiaobo Li3, Xishan Wang1, Huihui Fan2, Guiyu Wang1 and Dong Wang2,4
1 Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
2 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
3 Department of Pathology, Harbin Medical University, Harbin, China
4 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
* These authors have contributed equally to this work
Dong Wang, email:
Guiyu Wang, email:
Huihui Fan, email:
Xishan Wang, email:
Keywords: colorectal cancer, colitis, crosstalk, pivot, network analysis
Received: August 16, 2015 Accepted: September 24, 2015 Published: October 10, 2015
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.
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