Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice

BMC Cancer

Ahmed Hammad¹  Xiuwen Tang¹  Mohamed Elshaer¹  Akhileshwar Namani²  Xiu Jun Wang³  Zhao-Hong Zheng³ 

[1] Department of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, People’s Republic of China;Department of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, People’s Republic of China;Present address: Department of Biotechnology, Institute of Science, GITAM, 530045, Visakhapatnam, India;Department of Pharmacology, Zhejiang University School of Medicine, Zhejiang University, 310058, Hangzhou, People’s Republic of China;

关键词: Mkp-1;    Colitis;    Colorectal cancer;    RNA sequencing;    Biomarker;   

DOI  :  10.1186/s12885-021-08200-0

来源: Springer

【 摘 要 】

BackgroundThe nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis.MethodsAzoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software.ResultsPersistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified.ConclusionThese findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation.Graphical abstract

【 授权许可】

CC BY