Evidence map›Paper›PMID 41430564›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Microbial metabolite 5-formamidoimidazole-4-carboxamide ribotide targets METTL1 to inhibit m7G modification of BRCA1 mRNA to inhibit high-grade serous ovarian cancer.

Lixing Chen, Sili He

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Lixing ChenDepartment of Gynecology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, China.
Sili HeDepartment of Gynecology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, China. hesili@csu.edu.cn.ORCID 0009-0002-5738-8803

Funding

Changsha Natural Science Foundation kq2403053
6 · The paper itself

Abstract

backgroundThis study explored the impact of vaginal microbes, metabolites, and METTL1-mediated m7G modification of BRCA1 mRNA on High-Grade Serous Ovarian Cancer (HGSOC).

methodsMETTL1 and BRCA1 expression levels were assessed via bioinformatics, Western blotting, and RT-qPCR. Their interaction was studied using RNA co-immunoprecipitation and RNA pull-down assays. The functions and mechanisms of METTL1 and BRCA1 in HGSOC were investigated through CCK-8 assays, flow cytometry, transwell migration assays, and nude mouse xenograft models. We analyzed vaginal microbial and metabolite differences in HGSOC patients with varying BRCA1 expression using 16 S rRNA sequencing and liquid chromatography. Associations were evaluated with Spearman correlation and heat maps, while molecular docking assessed key metabolite binding to METTL1. The roles and interactions of selected metabolites with METTL1/BRCA1 in HGSOC were validated through in vivo and in vitro experiments.

resultsIn HGSOC, both METTL1 and BRCA1 were up-regulated. METTL1 enhanced BRCA1 expression via m7G modification, boosting cell proliferation and tumor growth. Elevated BRCA1 levels were associated with changes in vaginal microbiota, particularly increased Lactobacillus, and alterations in metabolic pathways. Correlation analysis indicated that Lactobacillus was significantly negatively correlated with 5-formamidoimidazole-4-carboxamide ribotide, inosine, cobalt-precorrin-7, and uridine, but positively correlated with L-lysine. The strongest correlation was with 5-formamidoimidazole-4-carboxamide ribotide. Molecular docking showed that this compound binds strongly to METTL1. Functional tests demonstrated that it inhibits HGSOC cell proliferation and tumor growth by disrupting METTL1-mediated m7G modification of BRCA1. Overexpression of METTL1 or BRCA1 negated its anti-tumor effects.

conclusionThe vaginal microbial metabolite 5-formamidoimidazole-4-carboxamide ribotide reduces BRCA1 expression and slows HGSOC progression by modifying BRCA1 m7G through METTL1, suggesting its potential as an HGSOC treatment.

Indexed as

BRCA1 ProteinCystadenocarcinoma, SerousMethyltransferasesOvarian NeoplasmsRNA, MessengerAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeMolecular Docking SimulationXenograft Model Antitumor AssaysBRCA1 ProteinBRCA1 protein, humanMethyltransferasesRNA, MessengerBRCA1High-grade serous ovarian cancerm7GMETTL1Microbial metabolite

Identifiers

PMID41430564
PMCPMC12825273

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