Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39279957", "kind": "science-record", "revision": 4, "content_hash": "sha256:3e4480752c5744e24c8b141b9e353d383fab90ef6db7ac0a3bf7202eac027853", "created_at": "2026-11-01T20:29:26Z", "updated_at": "2026-11-01T22:55:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology.", "doi": "10.21037/jgo-24-413", "pmid": "39279957", "authors": ["Ziming Zhu", "Yinbiao Zhang", "Xinyue Zhang", "Qiaoling Chen", "Shanneng Tang", "Xuan Zhou", "Xiao Li", "Jieying Wen", "Yang Bai", "Tao Zhang"], "journal": "Journal of gastrointestinal oncology", "year": 2024, "abstract": "Background: Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, posing a significant clinical challenge due to its complex tumor microenvironment (TME) and metabolic heterogeneity. Despite continuous improvements in treatment strategies including surgery, chemotherapy, and targeted therapies, the metabolic reprogramming in GC continues to impede treatment efficacy, highlighting an urgent need for the development of novel therapeutic strategies. This persistent issue underscores the urgent need for novel therapeutic approaches that can effectively address the diverse and dynamic characteristics of GC. Cimifugin, a traditional Chinese medicine (TCM), has garnered attention for its potential role in alleviating inflammation, neurological disorders, pain, and metabolic disorders. Its multi-targeting properties and minimal side effects suggest a broad potential for cancer management, which is currently being explored. This study aims to delineate the molecular mechanisms that cimifugin may impact within the TME and metabolic pathways of GC, with the expectation of contributing to a deeper understanding of GC and the development of innovative treatment strategies.\nMethods: We identified the GC-related TME cell types and metabolic profiles and pathways by using relevant data from the single-cell RNA sequencing (scRNA-seq) database GSE134520 and the stomach adenocarcinoma (STAD) data set from The Cancer Genome Atlas (TCGA). We also assessed the effects of cimifugin on MKN28 cell proliferation, invasion, and migration. By using six public platforms, we comprehensively predicted the potential biological targets of cimifugin. Clinical prognosis and immunohistochemistry (IHC), molecular docking, and dynamics simulations were used to confirm the clinical relevance and stability of the aforementioned targets.\nResults: Cimifugin inhibited MKN28 cell proliferation, migration, and invasion. Cimifugin may potentially act on various metabolic pathways in GC, including folate biosynthesis, xenobiotic metabolism via cytochrome P450 (CYP), glutathione metabolism, steroid hormone biosynthesis, and tryptophan metabolism. Cimifugin was noted to stably bind to three significant core targets associated with metabolic reprogramming in GC: AKR1C2, MAOB, and PDE2A; all three targets were strongly expressed in endocrince cells, pit mucous cells (PMCs), and common myeloid progenitors (CMPs).\nConclusions: We verified the pharmacological effects of cimifugin on GC cell proliferation, invasion, and migration. AKR1C2, MAOB, and PDE2A were identified as the key targets of cimifugin in GC-related metabolic reprogramming and pathogenesis. Our research provides preliminary insights into the potential therapeutic effects of cimifugin, which could be considered for future exploration in the context of GC treatment.", "claims": [{"id": "claim-method", "statement": "Our quantitative results, expressed as mean ± standard deviation, were compared between multiple groups by using one-way analysis of variance (ANOVA) with a test level of α=0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39279957", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Our quantitative results, expressed as mean ± standard deviation, were compared between multiple groups by using one-way analysis of variance (ANOVA) with a test level of α=0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-413/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39279957", "locator": "sections[43] \"Data Sharing Statement\" paragraph 2", "quote": "Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-413/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Cimifugin inhibited MKN28 cell proliferation, migration, and invasion.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39279957", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Cimifugin inhibited MKN28 cell proliferation, migration, and invasion."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Cimifugin inhibited MKN28 cell proliferation, migration, and invasion.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39279957"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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