Fusobacterium Nucleatum Promotes Microsatellite Instability in Colorectal Carcinoma Through Up-regulation of miRNA-155-5p-Targeted Inhibition of MSH6 via the TLR4/NF-κB Signaling Pathway
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View abstract on PubMed
Summary
This summary is machine-generated.Fusobacterium nucleatum (Fn) drives colorectal cancer (CRC) progression by activating TLR4/NF-κB signaling, upregulating miRNA-155-5p, and inhibiting MSH6, impacting microsatellite instability (MSI). This pathway accelerates CRC in mice but can be blocked by miRNA-155-5p antagomirs.
Area Of Science
- Microbiology
- Oncology
- Molecular Biology
Background
- Fusobacterium nucleatum (Fn) is linked to poor colorectal carcinoma (CRC) prognosis.
- The mechanisms of Fn's influence on DNA mismatch repair (MMR) and microsatellite instability (MSI) in CRC remain unclear.
Purpose Of The Study
- To investigate the relationship between Fn abundance and microsatellite stability in CRC.
- To elucidate the molecular mechanisms by which Fn affects CRC progression, focusing on the TLR4/Myd88/NF-κB pathway and MSH6 regulation.
Main Methods
- Analysis of clinical CRC samples for Fn abundance and microsatellite stability.
- In vitro experiments treating CRC cells with Fn to assess protein expression (TLR4, Myd88, MSH6, NF-κB).
- In vivo studies using a nude mouse tumor model to evaluate Fn's effect on CRC development and the impact of miRNA-155-5p antagomirs.
Main Results
- MSI-type CRC patients exhibited higher Fn abundance compared to microsatellite stability (MSS)-type.
- Fn treatment activated the TLR4/Myd88/NF-κB pathway, inducing miRNA-155-5p expression and downregulating MSH6.
- Fn accelerated CRC progression in mice, an effect reversed by miRNA-155-5p antagomirs.
Conclusions
- Fn upregulates miRNA-155-5p via TLR4/NF-κB signaling, inhibiting MSH6 and potentially affecting CRC microsatellite stability.
- This regulatory pathway contributes to CRC malignant progression and presents a potential therapeutic target.
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