MiR-224-5p regulates chemoresistance in colorectal cancer via Bcl-2-mediated autophagy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40523762", "kind": "science-record", "revision": 4, "content_hash": "sha256:6093a35bc92ab27a2ab9adc328add284fcbd7e38208c9e7d67658aaee6f42e1d", "created_at": "2026-11-01T20:30:37Z", "updated_at": "2026-11-01T22:56:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MiR-224-5p regulates chemoresistance in colorectal cancer via Bcl-2-mediated autophagy.", "doi": "10.11817/j.issn.1672-7347.2025.240243", "pmid": "40523762", "authors": ["Hui Zhou", "Meng Wu", "Shaihong Zhu", "Yi Zhang"], "journal": "Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences", "year": 2025, "abstract": "OBJECTIVES: Oxaliplatin (OXA) and 5-fluorouracil (5-FU) are 2 commonly used chemotherapeutic agents for colorectal cancer (CRC). MicroRNAs (miRNAs, miRs) play crucial roles in the development of chemoresistance in various cancers. However, the role and mechanism of miR-224-5p in regulating CRC chemoresistance remain unclear. This study aims to investigate the function of miR-224-5p in chemoresistant CRC cells and the underlying mechanisms.\nMETHODS: CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs between drug-sensitive and resistant groups (OXA or 5-FU) were analyzed, and miR-224-5p was identified as the target miRNA. Chemoresistant cell lines HCT15-OXR, HCT15-5-FU, SW480-OXR, and SW480-5-FU were established. Transient transfections were performed using miR-224-5p mimics, inhibitors, and their respective negative controls (control mimic, control inhibitor) in these cell lines. Cells were treated with different concentrations of OXA or 5-FU post-transfection, and the half-maximal inhibitory concentration (IC50) was determined using the cell counting kit-8 (CCK-8) assay. Cell proliferation was assessed by CCK-8 and colony formation assays. The expression levels of miR-224-5p, LC3, and P62 were measured by real-time polymerase chain reaction (real-time PCR) and/or Western blotting. Autophagic flux was assessed using a tandem fluorescent-tagged LC3 reporter assay. TargetScan 8.0, miRTarBase, miRPathDB, and HADb were used to predict B-cell lymphoma-2 (Bcl-2) as a potential miR-244-5p target, which was further validated by dual-luciferase reporter assays.\nRESULTS: Chemoresistant CRC cells exhibited down-regulated miR-224-5p expression, whereas up-regulation of miR-224-5p enhanced chemotherapy sensitivity. Exposure to OXA or 5-FU significantly increased autophagic activity in chemoresistant CRC cells, which was reversed by miR-224-5p overexpression. Dual-luciferase assays verified Bcl-2 as a direct target of miR-224-5p.\nCONCLUSIONS: MiR-224-5p regulates chemoresistance in CRC by modulating autophagy through direct targeting of Bcl-2.", "claims": [{"id": "claim-method", "statement": "Statistical comparisons were performed using either Student’s t-test or one-way ANOVA, as appropriate for the experimental design. Intergroup correlations were assessed using Pearson’s correlation coefficient, while survival outcomes were evaluated through Kaplan-Meier analysis with log-rank tests for comparing survival differences.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40523762", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Statistical comparisons were performed using either Student’s t-test or one-way ANOVA, as appropriate for the experimental design. Intergroup correlations were assessed using Pearson’s correlation coefficient, while survival outcomes were evaluated through Kaplan-Meier analysis with log-rank tests for comparing survival differences."}], "state": "complete"}, {"id": "claim-data-access", "statement": "CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus (GEO) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40523762", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus (GEO) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Analysis of differentially expressed miRNAs in drug-sensitive and resistant CRC groups identified miR-224-5p as the target miRNA.", "kind": "quantitative", "target": {"value": 5.0, "unit": "odds ratio", "tolerance": null, "source": "Differentially expressed miRNAs between drug-sensitive and resistant groups (OXA or 5-FU) were analyzed, and miR-224-5p was identified as the target miRNA."}, "evidence": [{"asset": "source:pmid:40523762", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed miRNAs between drug-sensitive and resistant groups (OXA or 5-FU) were analyzed, and miR-224-5p was identified as the target miRNA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Analysis of differentially expressed miRNAs in drug-sensitive and resistant CRC groups identified miR-224-5p as the target miRNA.", "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:40523762"], "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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