Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

Humans Fusobacterium nucleatum / genetics Matrix Metalloproteinase 7 / genetics Colorectal Neoplasms / pathology Molecular Docking Simulation Fusobacterium Infections / complications
Colorectal cancer Fusobacterium nucleatum Matrix metalloproteinase 7 Migration

Journal

Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741

Informations de publication

Date de publication:
09 10 2023
Historique:
received: 26 02 2023
accepted: 15 09 2023
medline: 11 10 2023
pubmed: 10 10 2023
entrez: 9 10 2023
Statut: epublish

Résumé

Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Sections du résumé

BACKGROUND
Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated.
METHODS
Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking.
RESULTS
F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC.
CONCLUSIONS
Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Identifiants

DOI: 10.1186/s12967-023-04527-3 PMID: 37814323 PMC: PMC10561506
pubmed: 37814323
doi: 10.1186/s12967-023-04527-3
pii: 10.1186/s12967-023-04527-3
pmc: PMC10561506
doi:

Substances chimiques

Matrix Metalloproteinase 7 EC 3.4.24.23
MMP7 protein, human EC 3.4.24.23

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

704

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Suwen Ou (S)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
ORCID: 0000-0002-5540-2192

Haipeng Chen (H)

Department of Colorectal Surgery, National Clinical Research Center of Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Hufei Wang (H)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Jinhua Ye (J)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Huidi Liu (H)

Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China.

Yangbao Tao (Y)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Songlin Ran (S)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Xiaoqin Mu (X)

Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China.

Fangzhou Liu (F)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Shuang Zhu (S)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Kangjia Luo (K)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Department of Gastrointestinal Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China.

Zilong Guan (Z)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.

Yinghu Jin (Y)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

Rui Huang (R)

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. huangrui2019@163.com.

Yanni Song (Y)

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China. yannimd@126.com.

Shu-Lin Liu (SL)

Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. slliu@hrbmu.edu.cn.
Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China. slliu@hrbmu.edu.cn.
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 4N1, Canada. slliu@hrbmu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Fusobacterium nucleatum upregulates MMP7 to...
questionsmedicales.fr › Bactéries › Bactéries à Gram négatif › Bactéries anaérobies à Gram négatif › Bâtonnets à Gram négatif anaérobies droits, incurvés et spiralés › Fusobacterium › Fusobacterium nucleatum › Fusobacterium nucleatum upregulates MMP7 to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Secreted matrix metalloproteinases › Matrix metalloproteinase 7 › Fusobacterium nucleatum upregulates MMP7 to...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › Fusobacterium nucleatum upregulates MMP7 to...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de docking moléculaire › Fusobacterium nucleatum upregulates MMP7 to...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram négatif › Infections à Fusobacteriaceae › Infections à Fusobacterium › Fusobacterium nucleatum upregulates MMP7 to...