LINC01559 drives osimertinib resistance in NSCLC through a ceRNA network regulating miR-320a/IGF2BP3 axis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40313617", "kind": "science-record", "revision": 4, "content_hash": "sha256:fe221d805df53eb710d13b21749fac07d2992035795ac4cbb512d28b81008231", "created_at": "2026-11-01T20:30:28Z", "updated_at": "2026-11-01T22:56:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "LINC01559 drives osimertinib resistance in NSCLC through a ceRNA network regulating miR-320a/IGF2BP3 axis.", "doi": "10.3389/fphar.2025.1592846", "pmid": "40313617", "authors": ["Leidi Xu", "Yibo Zhang", "Liangliang Xing", "Ying Zhou", "Ning Chang", "Hangtian Xi", "Xiangrui Xu", "Jian Zhang"], "journal": "Frontiers in pharmacology", "year": 2025, "abstract": "Background: Osimertinib resistance remains a major challenge in the treatment of lung adenocarcinoma. Long non-coding RNAs (lncRNAs) have emerged as key regulators of drug resistance, but their roles in osimertinib resistance are poorly understood. This study aimed to identify lncRNAs driving osimertinib resistance and elucidate their molecular mechanisms.\nMethods: Multi-cohort analysis (GSE222820, GSE232890, GSE255958) identified osimertinib resistance-associated lncRNAs. Functional validation employed in vitro assays (proliferation, migration, invasion, drug sensitivity) and xenograft models. Mechanistic studies involved luciferase reporter assays, RNA immunoprecipitation (RIP), and Western blotting. Clinical correlations were analyzed using TCGA-LUAD data.\nResults: Our findings demonstrated that LINC01559 was markedly upregulated in LUAD tissues and osimertinib-resistant cell lines, correlating with poor patient survival. Functional analyses revealed that LINC01559 critically regulates processes linked to drug resistance, enhancing tumor cell proliferation, migration, and invasive capabilities. Knockdown of LINC01559 sensitized resistant cells to osimertinib, significantly reducing colony-forming potential and suppressing migratory/invasive behaviors. In contrast, overexpression of LINC01559 exacerbated therapeutic resistance. Mechanistically, LINC01559 functions as a competing endogenous RNA (ceRNA) by sponging miR-320a, promote osimertinib -resistance and upregulate the expression of the miR-320a target IGF2BP3. Rescue experiments and xenograft models confirmed that Linc01559 drives resistance via the miR-320a/IGF2BP3 axis.\nConclusion: This study identifies LINC01559 as a novel ceRNA that drives osimertinib resistance in lung adenocarcinoma by sponging miR-320a to enhance IGF2BP3 expression. Targeting the LINC01559/miR-320a/IGF2BP3 axis may provide a therapeutic strategy to overcome osimertinib resistance.", "claims": [{"id": "claim-method", "statement": "Differentially expressed lncRNAs (DELs) in osimertinib-resistant cells and osimertinib-sensitive cells were identified from three public transcriptomic datasets (GSE222820, GSE232890, GSE255958) using DESeq2 and limma R package (|log2 fold change| >1, adjusted p < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40313617", "locator": "sections[15] \"Bioinformatics analysis and target gene prediction\" paragraph 2", "quote": "Differentially expressed lncRNAs (DELs) in osimertinib-resistant cells and osimertinib-sensitive cells were identified from three public transcriptomic datasets (GSE222820, GSE232890, GSE255958) using DESeq2 and limma R package (|log2 fold change| >1, adjusted p < 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE222820 https://www.ncbi.nlm.nih.gov/geo/, GSE232890 https://www.ncbi.nlm.nih.gov/geo/, GSE255958.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40313617", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE222820 https://www.ncbi.nlm.nih.gov/geo/, GSE232890 https://www.ncbi.nlm.nih.gov/geo/, GSE255958."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The LINC01559/miR-320a/IGF2BP3 axis drives osimertinib resistance in lung adenocarcinoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40313617", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study identifies LINC01559 as a novel ceRNA that drives osimertinib resistance in lung adenocarcinoma by sponging miR-320a to enhance IGF2BP3 expression."}, {"asset": "source:pmid:40313617", "locator": "sections[22] \"The LINC01559/miR-320a/IGF2BP3 axis promotes osimertinib resistance in vitro and in vivo\" paragraph 5", "quote": "These findings collectively establish the LINC01559/miR-320a/IGF2BP3 axis as a critical driver of tumor growth and osimertinib resistance, highlighting its potential as a therapeutic target in NSCLC (Figure 6)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The LINC01559/miR-320a/IGF2BP3 axis drives osimertinib resistance in lung adenocarcinoma.", "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:40313617"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE222820"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE222820"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40313617", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2025.1592846", "sha256": "sha256:403eb000cab9a562fb16ba72f2059003358a1750d18ebde211a20b5785ca080c", "bytes": 53696, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2025.1592846", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12043721", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE222820", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE222820", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE222820", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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