Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice
Abstract Background The 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 inflamma...
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doaj-8b1680c8f4f749229317cc398375742b2021-05-30T11:49:36ZengBMCBMC Cancer1471-24072021-05-0121111310.1186/s12885-021-08200-0Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient miceAhmed Hammad0Zhao-Hong Zheng1Akhileshwar Namani2Mohamed Elshaer3Xiu Jun Wang4Xiuwen Tang5Department of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pharmacology, Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pharmacology, Zhejiang University School of Medicine, Zhejiang UniversityDepartment of Biochemistry and Department of Thoracic Surgery of The First Affiliated Hospital, Zhejiang University School of MedicineAbstract Background The 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. Methods Azoxymethane/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. Results Persistent 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. Conclusion These 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 abstracthttps://doi.org/10.1186/s12885-021-08200-0Mkp-1ColitisColorectal cancerRNA sequencingBiomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ahmed Hammad Zhao-Hong Zheng Akhileshwar Namani Mohamed Elshaer Xiu Jun Wang Xiuwen Tang |
spellingShingle |
Ahmed Hammad Zhao-Hong Zheng Akhileshwar Namani Mohamed Elshaer Xiu Jun Wang Xiuwen Tang Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice BMC Cancer Mkp-1 Colitis Colorectal cancer RNA sequencing Biomarker |
author_facet |
Ahmed Hammad Zhao-Hong Zheng Akhileshwar Namani Mohamed Elshaer Xiu Jun Wang Xiuwen Tang |
author_sort |
Ahmed Hammad |
title |
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice |
title_short |
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice |
title_full |
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice |
title_fullStr |
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice |
title_full_unstemmed |
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice |
title_sort |
transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of mkp-1-deficient mice |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2021-05-01 |
description |
Abstract Background The 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. Methods Azoxymethane/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. Results Persistent 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. Conclusion These 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 |
topic |
Mkp-1 Colitis Colorectal cancer RNA sequencing Biomarker |
url |
https://doi.org/10.1186/s12885-021-08200-0 |
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