Identification of Novel Core Genes Involved in Malignant Transformation of Inflamed Colon Tissue Using a Computational Biology Approach and Verification in Murine Models Full article
| Journal |
International Journal of Molecular Sciences
, E-ISSN: 1422-0067 |
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| Output data | Year: 2023, Volume: 24, Article number : 4311, Pages count : DOI: 10.3390/ijms24054311 | ||
| Tags | colitis; colitis-associated cancer; inflammatory bowel disease; colorectal cancer; colon adenocarcinoma; ulcerative colitis; Crohn’s disease; cDNA microarray; transciptomics analysis; microarray | ||
| Authors |
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| Affiliations |
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Funding (2)
| 1 | МИНИСТЕРСТВО НАУКИ И ВЫСШЕГО ОБРАЗОВАНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ | ПФНИ РФ (2021-2030) 0245-2021-0004 |
| 2 | Russian Science Foundation | РНФ №19-74-30011 |
Abstract:
: Inflammatory bowel disease (IBD) is a complex and multifactorial systemic disorder of
the gastrointestinal tract and is strongly associated with the development of colorectal cancer.
Despite extensive studies of IBD pathogenesis, the molecular mechanism of colitis-driven
tumorigenesis is not yet fully understood. In the current animal-based study, we report a
comprehensive bioinformatics analysis of multiple transcriptomics datasets from the colon tissue of
mice with acute colitis and colitis-associated cancer (CAC). We performed intersection of
differentially expressed genes (DEGs), their functional annotation, reconstruction, and topology
analysis of gene association networks, which, when combined with the text mining approach,
revealed that a set of key overexpressed genes involved in the regulation of colitis (C3, Tyrobp,
Mmp3, Mmp9, Timp1) and CAC (Timp1, Adam8, Mmp7, Mmp13) occupied hub positions within
explored colitis- and CAC-related regulomes. Further validation of obtained data in murine models
of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-stimulated CAC fully
confirmed the association of revealed hub genes with inflammatory and malignant lesions of colon
tissue and demonstrated that genes encoding matrix metalloproteinases (acute colitis: Mmp3,
Mmp9; CAC: Mmp7, Mmp13) can be used as a novel prognostic signature for colorectal neoplasia in
IBD. Finally, using publicly available transcriptomics data, translational bridge interconnecting of
listed colitis/CAC-associated core genes with the pathogenesis of ulcerative colitis, Crohn’s disease,
and colorectal cancer in humans was identified. Taken together, a set of key genes playing a core
function in colon inflammation and CAC was revealed, which can serve both as promising
molecular markers and therapeutic targets to control IBD and IBD-associated colorectal neoplasia.
Cite:
Markov A.V.
, Savin I.A.
, Zenkova M.A.
, Sen'kova A.V.
Identification of Novel Core Genes Involved in Malignant Transformation of Inflamed Colon Tissue Using a Computational Biology Approach and Verification in Murine Models
International Journal of Molecular Sciences. 2023. V.24. 4311 . DOI: 10.3390/ijms24054311 WOS Scopus PMID OpenAlex
Identification of Novel Core Genes Involved in Malignant Transformation of Inflamed Colon Tissue Using a Computational Biology Approach and Verification in Murine Models
International Journal of Molecular Sciences. 2023. V.24. 4311 . DOI: 10.3390/ijms24054311 WOS Scopus PMID OpenAlex
Dates:
| Published print: | Feb 21, 2023 |
Identifiers:
| Web of science: | WOS:000947516400001 |
| Scopus: | 2-s2.0-85149886019 |
| PMID: | 36901742 |
| OpenAlex: | W4321523308 |