FadA antigen of Fusobacterium nucleatum: implications for ceRNA network in colorectal cancer and adenomatous polyps progression Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study investigated the impact of Fusobacterium nucleatum’s FadA antigen on the competing endogenous RNA (ceRNA) network involving ANXA2 (Annexin A2) and its role in the progression of colorectal cancer (CRC) and adenomatous polyps (AP). Specifically, it examined how the FadA antigen contributes to the upregulation of ANXA2 through interactions with LINC00460 and hsa-let-7a-2, and how these interactions affect CRC progression.
Who was studied?
The study analyzed tissue samples from 30 healthy controls (HC), 30 patients with adenomatous polyps (AP), and 30 patients with stage I colorectal cancer (CRC). The samples were obtained from colonic biopsies of patients who had no history of cancer or gastrointestinal diseases. In vitro, the expression levels of FadA, ANXA2, LINC00460, and miRNAs were assessed using qRT-PCR to observe the correlation between these molecules and CRC progression.
What were the most important findings?
The study found elevated expression levels of FadA, ANXA2, and LINC00460 in both AP and CRC tissues compared to normal tissues. The expression of hsa-let-7a-2 was notably decreased in both AP and CRC samples. A significant positive correlation was observed between FadA and LINC00460 (r = 0.9311, p <0.0001), suggesting that FadA promotes the upregulation of LINC00460. This, in turn, enhances the expression of ANXA2, which is involved in regulating key cellular processes such as migration, adhesion, and invasion in CRC. Functional analysis revealed that ANXA2 plays a crucial role in CRC progression by affecting the JAK-STAT and Hippo signaling pathways, which are associated with cell proliferation and metastasis. Additionally, the study validated the constructed ceRNA network and confirmed that FadA induces CRC progression through the modulation of these molecular interactions, linking microbiome factors with gene expression in CRC.
What are the greatest implications of this study?
The findings suggest that Fusobacterium nucleatum plays a significant role in CRC progression through the FadA antigen’s impact on the ANXA2 ceRNA network. Targeting this network, specifically FadA or ANXA2, could offer a novel therapeutic strategy for preventing or treating CRC. The study highlights the potential of LINC00460 as an oncogenic long noncoding RNA and miRNA regulators like hsa-let-7a-2 as biomarkers for CRC detection and progression. Furthermore, understanding how FadA influences CRC through the ceRNA network may help identify additional molecular targets and improve therapeutic approaches in managing both adenomatous polyps and CRC.
Fusobacterium nucleatum
Fusobacterium nucleatum is a Gram-negative, anaerobic bacterium commonly found in the oral cavity, where it plays a crucial role in the formation of biofilms. Beyond its presence in the mouth, Fn is implicated in a variety of systemic conditions, including periodontal disease, colorectal cancer, and inflammatory bowel disease. Known for its ability to coaggregate with other bacteria, Fn's pathogenic potential is magnified in dysbiotic microbial communities, making it a key player in polymicrobial infections. The bacterium utilizes multiple virulence factors such as FadA and Fap2, which facilitate adhesion to host tissues and immune evasion, ultimately contributing to its role in chronic and inflammatory diseases.