Evidence map›Paper›PMID 40924735›Full record

ArticlePloS one2025

Integrative network toxicology and molecular docking reveal 4-Nonylphenol's multifaceted mechanisms in breast cancer pathogenesis.

Congli Jia, Fu Yang

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Congli JiaDepartment of Plastic Surgery, Plastic Surgery Hospital of Shandong Second Medical University, Weifang, Shandong, China.ORCID 0000-0002-7090-6364
Fu YangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study employs integrated network toxicology and molecular docking to investigate the molecular basis underlying 4-nonylphenol (4-NP)-mediated enhancement of breast cancer susceptibility.

methodsWe integrated data from multiple databases, including ChEMBL, STITCH, Swiss Target Prediction, GeneCards, OMIM and TTD. Core compound-disease-associated target genes were identified through Protein-Protein Interaction (PPI) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were subsequently employed to elucidate the potential molecular functions and biological pathways associated with these key targets. Molecular docking using AutoDock Vina was conducted to investigate the binding interactions between the core genes and 4-NP. Furthermore, the miRDB database was utilized to identify potential microRNAs (miRNAs) that may exert regulatory control over the pivotal genes.

resultsFive hub breast cancer target genes associated with 4-NP exposure were screened, containing TP53, HDAC1, ESR1, CTNNB1 and MYC. GO and KEGG analyses revealed that intersecting genes mainly influenced PI3K-Akt signaling, MicroRNAs in cancer, Chemical carcinogenesis-receptor activation and MAPK signaling. Molecular docking confirmed strong binding affinities of 4-NP to these hub genes. Subsequently several high-confidence candidate regulatory miRNAs especially miR-22, -148a, -181a and -152 were identified that shed light on miRNA regulatory mechanisms by which 4-NP increases breast cancer risk.

conclusionOur study demonstrates that 4-NP exposure perturbs protein conformational of hub targets, activating cascades and dysregulating signaling pathway to potentiate breast cancer risk. Furthermore, we identify a novel miRNA-mediated regulatory axis alongside MAPK signaling as critical mechanisms underpinning 4-NP toxicity.

Indexed as

Breast NeoplasmsMolecular Docking SimulationPhenolsFemaleGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMicroRNAsProtein Interaction MapsSignal Transduction4-nonylphenolMicroRNAsPhenols

Identifiers

PMID40924735
PMCPMC12419657

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.