miR-125b-5p upregulation by TRIM28 induces cisplatin resistance in non-small cell lung cancer through CREB1 inhibition.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36476351", "kind": "science-record", "revision": 2, "content_hash": "sha256:17d413bd74a2654fb59dffa31335faf95ff0081978dd7448b49a2fb2656b0dd5", "created_at": "2026-11-01T19:00:58Z", "updated_at": "2026-11-01T21:29:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "miR-125b-5p upregulation by TRIM28 induces cisplatin resistance in non-small cell lung cancer through CREB1 inhibition.", "doi": "10.1186/s12890-022-02272-9", "pmid": "36476351", "authors": ["Qiuyu Tan", "Jinzhu Ma", "Hao Zhang", "Xu Wu", "Qiang Li", "Xiaoxuan Zuo", "Yuxin Jiang", "Haijun Liu", "Liang Yan"], "journal": "BMC pulmonary medicine", "year": 2022, "abstract": "OBJECTIVE: miR-125b-5p plays an important role in the development of cancer and drug resistance. However, in cisplatin resistance of non-small cell lung cancer (NSCLC), the function and potential mechanism of miR-125b-5p is still unclear. The aim of this study was to investigate the role and molecular mechanism of miR-125b-5p in cisplatin resistance of NSCLC.\nMETHODS: A GEO dataset (GSE168707) was analyzed to find high miR-125b-5p levels were associated with DDP resistance. miR-125b-5p expression levels were detected in A549 and A549/DDP cells via real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays, western blots and mouse model xenografted were performed to identify CREB1 as a direct target gene of miR-125b-5p. Cell proliferation and apoptosis were also performed to identify whether miR-125b-5p upregulation by TRIM28 induces DDP resistance in NSCLC through CREB1 inhibition.\nRESULTS: In A549/DDP cells, miR-125b-5p expression was upregulated compared to A549 cells. Then miR-125b-5p was found to increase DDP resistance in NSCLC in vivo and in vitro by increasing cell proliferation and suppressing cell apoptosis. Bioinformatic analyses were used to search for gene which miR-125b-5p can target. We identified miR-125b-5p can regulate CREB1 via luciferase reporter assays, qRT-PCR and western blots. Cell proliferation and apoptosis were also performed to confirm miR-125b-5p could impact on CREB1 and induce the DDP resistance in NSCLC. Additionally, we used bioinformatic analyses to find tripartite motif-containing 28 (TRIM28) as a transcriptional enhance factor of miR-125b-5p. The expression of TRIM28 was upregulated in A549/DDP cells compared with that in A549 cells by qRT-PCR. Finally, we found TRIM28 could mediate DDP resistance through miR-125b-5p/CREB1 axis via cell proliferation, western blot and apoptosis assay.\nCONCLUSIONS: Overall, our findings demonstrated novel functions and mechanisms underlying DDP resistance in NSCLC through the TRIM28/miR-125b-5p/CREB1 axis. These may serve as novel therapeutic targets to improve the treatment efficacy using DDP for NSCLC in the future.", "claims": [{"id": "claim-method", "statement": "Screening of DE-microRNAs was performed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/) with the criteria of adj.p.val < 0.01 and |log2 fold change (FC)| > 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36476351", "locator": "sections[3] \"Bioinformatics analysis of differentially expressed (DE) miRNAs\" paragraph 2", "quote": "Screening of DE-microRNAs was performed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/) with the criteria of adj.p.val < 0.01 and |log2 fold change (FC)| > 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data are presented in the manuscript. 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RESULTS: In A549/DDP cells, miR-125b-5p expression was upregu", "5b-5p expression was upregulated compared to A549 cells. Then miR-125b-5p was found to increas"], "order_basis": "paper_text_order:601", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["T-PCR (qRT-PCR). Luciferase reporter assays, western blots and mouse model xenografted were performed t", "via luciferase reporter assays, qRT-PCR and western blots. Cell proliferation and apoptosis were also", "R-125b-5p/CREB1 axis via cell proliferation, western blot and apoptosis assay. CONCLUSIONS: Overall, o"], "order_basis": "paper_text_order:698", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["uciferase reporter assays, western blots and mouse model xenografted were performed to identify CREB1", "as found to increase DDP resistance in NSCLC in vivo and in vitro by increasing cell proliferatio", "uciferase reporter assays, western blots and mouse model xenografted were performed to identify"], "order_basis": "paper_text_order:716", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["gene of miR-125b-5p. Cell proliferation and apoptosis were also performed to identify whether miR-", "sing cell proliferation and suppressing cell apoptosis. Bioinformatic analyses were used to search", "CR and western blots. Cell proliferation and apoptosis were also performed to confirm miR-125b-5p c", "xis via cell proliferation, western blot and apoptosis assay. CONCLUSIONS: Overall, our findings de"], "order_basis": "paper_text_order:837", "id": "assay:4"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ysis of differentially expressed (DE) miRNAs Microarray data of microRNA expression profiles associa"], "order_basis": "paper_text_order:2292", "id": "assay:5"}]}