Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40993657", "kind": "science-record", "revision": 3, "content_hash": "sha256:7d163ef7c173be9aadbcee312a620398389db44fa2f7482f59bc4b604de2c050", "created_at": "2026-11-01T20:31:04Z", "updated_at": "2026-11-01T22:14:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.", "doi": "10.1186/s12967-025-07039-4", "pmid": "40993657", "authors": ["Amalia Luce", "Marco Bocchetti", "Alessia Maria Cossu", "Madhura S Tathode", "David J Boocock", "Clare Coveney", "Maria Preziosa Romano", "Maria Roberta De Iesu", "Ines Simeone", "Luigi Mele", "Giovanni Vitale", "Rossella Sperlongano", "Gabriella Misso", "Elisabetta A M Verderio", "Silvia Zappavigna", "Michele Caraglia"], "journal": "Journal of translational medicine", "year": 2025, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p enhances anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. Here, we investigated the molecular mechanisms underlying miR-423-5p function through a comprehensive proteomic approach.\nMETHODS: We generated an HCC cell line stably overexpressing miR-423-5p via lentiviral transduction. Total proteins were extracted from SNU-387 cells, enzymatically digested into peptides, and subsequently analysed by liquid chromatography-tandem mass spectrometry (LC-MS/M). Raw spectral data were processed and quantified using MaxQuant. Differentially expressed proteins (DEPs) were defined based on fold-change (|log2FC| ≥ 1) and false discovery rate (FDR < 0.05). The full proteomic dataset is available via the ProteomeXchange repository (identifier: PXD064869). Functional enrichment analysis of DEPs were performed using DAVID and Reactome. To assess clinical relevance, predicted and validated miR-423-5p targets were integrated with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset using GEPIA platform. Survival analyses were performed using the Kaplan-Meier method.\nRESULTS: Proteomic profiling identified 698 DEPs in miR-423-5p-overexpressing cells compared to controls with significant enrichment in metabolic pathways, related to purine/pyrimidine metabolism and gluconeogenesis. Integration with bioinformatic predictions and miRTarBase validation identified 43 DEPs as potential direct targets of miR-423-5p. Among these, seven proteins (ACACA, ANKRD52, DVL3, MCM5, MCM7, RRM2, SPNS1, and SRM) were significantly associated with patient prognosis in the TCGA-LIHC cohort. These targets were downregulated in miR-423-5p-overexpressing cells but upregulated in advanced-stage HCC tissues, suggesting a potential role for miR-423-5p in the regulation of HCC pathogenesis. Stage-specific expression analysis showed increased levels from stage I to III, followed by a decline at stage IV. Notably, we experimentally confirmed miR-423-5p-mediated suppression of MCM7, DVL3, IMPDH1, and SRM (SPEE), supporting their functional involvement in HCC progression.\nCONCLUSION: Overall, our findings support a tumour-suppressive role for miR-423-5p in HCC, mediated by modulation of metabolic pathways and suppression of oncogenic proteins. These results suggest that miR-423-5p and its downstream effectors may serve as promising biomarkers and potential therapeutic targets in HCC.\nHIGHLIGHTS: miR-423-5p acts as a tumor suppressor in HCC by targeting key nodes of pro-tumorigenic signalling. miR-423-5p significantly altered metabolic pathways, including purine/pyrimidine metabolism and gluconeogenesis. Seven miR-423-5p targets correlate with poor prognosis in TCGA-LIHC patients and are downregulated in miR-423-5p overexpressing HCC cells. miR-423-5p over-expression induces a significant downregulation of MCM7, DVL3, IMPDH1, SPEE in HCC cell models. miR-423-5p limits tumor metabolic plasticity, suggesting therapeutic potential.", "claims": [{"id": "claim-method", "statement": "Survival analyses were performed using the Kaplan–Meier method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40993657", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Survival analyses were performed using the Kaplan–Meier method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All LC-MS/MS data generated in this study have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD064869 [56]. The other data supporting the findings of this study are available within the article and its supplementary materials.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40993657", "locator": "sections[22] \"notes\" paragraph 1", "quote": "All LC-MS/MS data generated in this study have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD064869 [56]. 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