Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 6, 2025

Abstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum ( F. , FN) being found in high abundance tissues. Previous research emphasized significant role of occurrence CRC. However, impact on CRC liver metastasis not well understood. Methods effects ability cell were evaluated vitro examined by wound-healing assay transwell assay. mouse model was constructed spleen injection, degree assessed vivo bioluminescence imaging. gene expression changes cells after co-culture analyzed through transcriptome sequencing. qRT-PCR Western Blot assays performed to validate related genes proteins. Results significantly enhanced vitro. In model, also promoted development Mechanistically, infection increased IL-8 downregulated level miR-5692a, a regulatory microRNA IL-8. This led activation ERK pathway resulted epithelial-mesenchymal transition (EMT) cells. Conclusions Our results suggest that promotes inducing miR-5692a/IL-8 axis. These findings provide new insights for prevention treatment metastasis.

Language: Английский

---

Microbiome-Driven Therapeutics: From Gut Health to Precision Medicine

Gastrointestinal Disorders, Journal Year: 2025, Volume and Issue: 7(1), P. 7 - 7

Published: Jan. 15, 2025

The human microbiome, a complex ecosystem of microorganisms residing in and on the body, plays pivotal role regulation wide range physiological processes, including digestion, immune responses, metabolic functions. In recent years, rapidly growing field microbiome-driven therapeutics has garnered significant attention owing to its potential revolutionize healthcare. This review explores evolving landscape microbiome-based therapies, with particular focus gut microbiome implications for both health precision medicine. We highlight advances understanding how microbial communities influence disease pathogenesis treatment outcomes, spanning conditions such as inflammatory bowel (IBD), disorders, neurological diseases, even cancer. article also discusses emerging therapeutic strategies, probiotics, prebiotics, fecal microbiota transplantation (FMT), microbial-based drugs, well challenges associated their clinical implementation. Additionally, we examined integration profiling metagenomic data is advancing medicine, paving way personalized effective treatments. serves comprehensive resource that synthesizes current knowledge, identifies key gaps research, offers insights into future direction therapeutics, thus providing valuable framework clinicians, researchers, policymakers seeking harness microbiomes advance healthcare solutions.

Language: Английский

---

HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(3)

Published: Feb. 2, 2025

Mutated tumor cells undergo changes in chromatin accessibility and gene expression, resulting aberrant proliferation differentiation, although how this occurs is unclear. HMGA1 regulators are abundant stem oncogenic diverse tissues; however, their role colon tumorigenesis only beginning to emerge. Here, we uncover a previously unknown epigenetic program whereby amplifies Wnt signaling during driven by inflammatory microbiota and/or Adenomatous polyposis coli (Apc) inactivation. Mechanistically, "opens" upregulate the cell regulator, Ascl2, downstream effectors, promoting Paneth-like states while depleting differentiated enterocytes. Loss of just one Hmga1 allele within epithelium restrains mutant Apc microbiota. However, deficiency has minimal effects under homeostatic conditions. In human cancer cells, directly induces ASCL2 recruiting activating histone marks. Silencing disrupts properties, whereas reexpression partially rescues these phenotypes. Further, coexpressed upregulated colorectal cancer. Together, our results establish as an gatekeeper signals state conditions APC inactivation, illuminating potential therapeutic target

Language: Английский

---

The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 676 - 676

Published: Feb. 5, 2024

Traditionally considered a disease common in the older population, colorectal cancer is increasing incidence among younger demographics. Evidence suggests that populational- and generational-level shifts composition of human gut microbiome may be tied to recent trends gastrointestinal carcinogenesis. This review provides an overview current research putative mechanisms behind rising with insight into future interventions prevent or reverse rate early-onset carcinoma.

Language: Английский

---

Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 29, 2024

Abstract Background Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent in world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) whole shotgun metagenomic to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) lesion patients (HRL), CRC cases, each sample sequenced using both methods. We thoroughly compared technologies at species, genus, family annotation levels, differences these taxa, sparsity, alpha beta diversities, ability train prediction models, similarity of microbial signature derived models. Results As expected, showed that detects only part gut community revealed shotgun, although some genera were profiled 16S. data was sparser exhibited lower diversity. In ranks, highly differed, partially due a disagreement reference databases. When considering shared positively correlated between two strategies. also found moderate correlation alpha-diversity measures, as well PCoAs. Regarding machine learning models degree predictive power an independent test set, but we could not demonstrate clear superiority one technology over other. Microbial signatures techniques taxa previously development, e.g., Parvimonas micra . Conclusions Shotgun provide different lenses examine communities. While have demonstrated they can unravel common patterns (including signatures), often gives more detailed snapshot than 16S, depth breadth. Instead, will tend show picture, giving greater weight dominant sample. Therefore, recommend choosing or another technique before launching study. Specifically, is preferred microbiome in-depth analyses, while suitable tissue studies targeted aims.

Language: Английский

---

Metabolic dysfunction-associated steatotic liver disease and extrahepatic gastrointestinal cancers

Metabolism, Journal Year: 2024, Volume and Issue: 160, P. 156014 - 156014

Published: Aug. 24, 2024

Language: Английский

---

Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Language: Английский

---

Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Jan. 16, 2024

Language: Английский

---

Emerging implications of bacterial biofilm in cancer biology: Recent updates and major perspectives

Gut Microbes Reports, Journal Year: 2024, Volume and Issue: 1(1), P. 1 - 20

Published: May 7, 2024

Recent insights have unveiled exciting opportunities to explore the intricate interplay among bacterial biofilms, tumor cells, and immune system, thus offering new perspectives in cancer biology. The implications of biofilms this context are remarkably multifaceted. Biofilms can promote growth invasiveness by inducing chronic inflammation, remodeling extracellular matrix, modulating response, which promotes development. findings demonstrated involvement distinct bacteria, like Salmonella typhi gall bladder cancer, Helicobacter pylori gastric Fusobacterium nucleatum oral cancer. These investigations indicate higher prevalence these bacteria individuals with as compared those who healthy. Additionally, create display resistance treatments.In review, we highlighted recent advancements pertaining influences biofilm progression potential molecular mechanisms contribute

Language: Английский

---

Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 20, 2024

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts digestive system, and closely linked to both genetic environmental factors. In CRC, mutations such as APC, KRAS, TP53, along with epigenetic changes like DNA methylation histone modifications, play crucial roles in tumor development treatment responses. This paper delves into complex biological underpinnings highlighting pivotal alterations, cell death pathways, intricate network signaling interactions that contribute disease's progression. explores dysregulation apoptosis, autophagy, other mechanisms, underscoring aberrant activation these pathways CRC. Additionally, examines how key molecular including Wnt, EGFR/MAPK, PI3K, fuel CRC development, alterations can serve diagnostic prognostic markers. The dual function autophagy acting suppressor promoter depending on context, also scrutinized. Through comprehensive analysis cellular events, this research aims deepen our understanding pave way for more effective diagnostics, prognostics, therapeutic strategies.

Language: Английский

---