Bladder cancer, inflammageing and microbiomes

Martin, Austin; Woolbright, Benjamin L.; Umar, Shahid; Ingersoll, Molly A.; Taylor, John A.

doi:10.1038/s41585-022-00611-3

Cited by 33 publications

(23 citation statements)

References 183 publications

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“…In the process of carcinogenesis, the intestinal microenvironment is changed; certain conditionally pathogenic bacteria proliferate preferentially; and the “driver” microorganisms are gradually replaced by these “passenger” microorganisms, thus promoting tumor progression. For BLCA, during the process, inflammation, immunity, and microbial dysbiosis are probable contributors to the known increase in cancer incidence [ 26 ]. For example, one indicator of systemic inflammation, serum neutrophil/lymphocyte ratio (NLR), was predictive of disease recurrence and progression in both NMIBC and MIBC [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the Fecal Metagenome and Metabolome in Bladder Cancer in a Chinese Population

Qin

Chen

Cao

et al. 2022

Genes

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Bladder cancer (BLCA) is a common malignancy of the urinary system. The gut microbiome produces various metabolites that play functional roles in tumorigenesis and tumor progression. However, the integrative analysis of the gut microbiome and metabolome in BLCA has still been lacking. Thus, the aim of this study was to identify microbial and functional characteristics and metabolites in BLCA in a Chinese population. Metagenomics, targeted metabolomics, bioinformatics, and integrative analysis were used in fecal samples of BLCA patients and healthy individuals. We found gut microbiomes were significantly dysregulated in BLCA patients, including Bifidobacterium, Lactobacillus, Streptococcus, Blautia, and Eubacterium. We also found 11Z-eicosenoic acid, 3-methoxytyrosine, abrine, aniline-2-sulfonate, arachidic acid, conjugated linoleic acids, elaidic acid, glycylleucine, glycylproline, leucyl-glycine, linoelaidic acid, linoleic acid, nicotinamide hypoxanthine dinucleotide, oleic acid, petroselinic acid, and ricinoleic acid to be significantly decreased, while cholesterol sulfate was significantly increased in BLCA patients. Integration of metagenomics and metabolomics revealed interactions between gut microbiota and metabolites and the host. We identified the alterations of gut microbiomes and metabolites in BLCA in a Chinese population. Moreover, we preliminarily revealed the associations between specific gut microbiomes and metabolites. These findings determined potential causative links among gut dysbiosis, dysregulated metabolites, and BLCA.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the Fecal Metagenome and Metabolome in Bladder Cancer in a Chinese Population

Qin

Chen

Cao

et al. 2022

Genes

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“…The main reason for the high mortality rate of patients with BCa is the recurrence and metastasis that occurs in some patients, even following treatment with conventional regimens ( 33 , 34 ). The mechanisms that are involved are complex.…”

Section: Discussionmentioning

confidence: 99%

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

Chen

Wang

et al. 2023

Oncol Rep

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The present study aimed to explore the potential roles of the methyltransferase-like 3 (METTL3)-mediated methylation of RAS related (RRAS) mRNA in the tumorigenesis and development of bladder cancer (BCa). For this purpose, the relative expression levels of METTL3 in BCa specimens and cell lines were measured using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. The association between the METTL3 expression level and the clinical characteristics of patients with BCa was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis databases. Cellular experiments were performed to confirm the effects of METTL3 on the proliferative, migratory and invasive capacities of BCa cells. RT-qPCR, western blot analysis, methylated RNA immunoprecipitation (MeRIP)-qPCR and dual-luciferase report assays were utilized to verify the METTL3/RRAS/YTH N 6 -methyladenosine (m6A) RNA binding protein 2 (YTHDF2) regulatory axis in BCa. The results revealed that METTL3 expression was markedly increased in BCa specimens and cell lines, and was associated with poor clinical characteristics of patients with BCa. In vitro and in vivo assays demonstrated that the silencing of METTL3 markedly suppressed the proliferative, migratory and invasive capacities of BCa cells. MeRIP-PCR and dual-luciferase report assays indicated that METTL3 could bind to the m6A sites of RRAS mRNA and suppress the transcriptional activity of RRAS. YTHDF2 could recognize the m6A sites of RRAS and mediate RRAS degradation. On the whole, the findings of the present study reveal the pivotal role of METTL3-catalyzed m6A modification in BCa tumorigenesis and development. The change could facilitate BCa tumor growth and metastasis by suppressing RRAS expression in an m6A YTHDF2-dependent manner. Targeting the METTL3/RRAS/YTHDF2 regulatory axis may thus prove to be a promising strategy for the diagnosis and therapy of BCa.

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“…It was found that Streptococcus was enriched in BC patients 157 . Owing to the microbiome diversity being affected by age, the microbiome is hard to be a powerful biomarker of BC 158 …”

Section: Urine Microbiome Biomarkers In Bcmentioning

confidence: 99%

“…157 Owing to the microbiome diversity being affected by age, the microbiome is hard to be a powerful biomarker of BC. 158…”

Section: Urine Microbiome Biomarkers In Bcmentioning

confidence: 99%

Recent development of urinary biomarkers for bladder cancer diagnosis and monitoring

Zeng

Wang

et al. 2023

Clinical and Translational Dis

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Urine‐based liquid biopsy has emerged as a non‐invasive and effective tool for early screening and diagnosis of bladder cancer. This review provides a comprehensive overview of the current urine‐based biomarkers and methods for the detection and monitoring of bladder cancer. We focus on biomarkers including tumour DNAs, proteins, microbiome, tumour RNAs, long non‐coding RNAs, transfer RNA‐derived fragments, messenger RNAs, microRNAs, circular RNAs, exosomes and extrachromosomal circular DNA.

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Bladder cancer, inflammageing and microbiomes

Cited by 33 publications

References 183 publications

Integrated Analysis of the Fecal Metagenome and Metabolome in Bladder Cancer in a Chinese Population

Integrated Analysis of the Fecal Metagenome and Metabolome in Bladder Cancer in a Chinese Population

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

Recent development of urinary biomarkers for bladder cancer diagnosis and monitoring

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