LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37173692", "kind": "science-record", "revision": 4, "content_hash": "sha256:5136973748ea621167281dd4ef209f6e34a99be6027364f6f43bde245634fc10", "created_at": "2026-11-01T19:01:50Z", "updated_at": "2026-11-01T22:51:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73.", "doi": "10.1186/s12967-023-04153-z", "pmid": "37173692", "authors": ["Yansu Wang", "Ming Liu", "Xiaoqian Liu", "Xianling Guo"], "journal": "Journal of translational medicine", "year": 2023, "abstract": "BACKGROUND: The ubiquitin protein ligase E3C (UBE3C) has been reported to play an oncogenic role in breast cancer (BRCA). This work further investigates the effect of UBE3C on the radioresistance of BRCA cells.\nMETHODS: Molecules linking to radioresistance in BRCA were identified by analyzing two GEO datasets, GSE31863 and GSE101920. UBE3C overexpression or knockdown was induced in parental or radioresistant BRCA cells, followed by irradiation treatment. The malignant properties of cells in vitro, and the growth and metastatic activity of cells in nude mice, were analyzed. Downstream target proteins, as well as upstream transcriptional regulators of UBE3C, were predicted by bioinformatics tools. Molecular interactions were confirmed by immunoprecipitation and immunofluorescence assays. Furthermore, artificial alterations of TP73 and FOSB were induced in the BRCA cells for functional rescue assays.\nRESULTS: According to bioinformatics analyses, UBE3C expression was linked to radioresistance in BRCA. UBE3C knockdown in radioresistant BRCA cells reduced while its overexpression in parental BRCA cells increased the radioresistance of cells in vitro and in vivo. UBE3C, which induced ubiquitination-dependent protein degradation of TP73, was transcriptionally activated by FOSB. The radioresistance of cancer cells was blocked by TP73 overexpression or FOSB knockdown. Additionally, LINC00963 was found to be responsible for the recruitment of FOSB to the UBE3C promoter for transcription activation.\nCONCLUSION: This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73.", "claims": [{"id": "claim-method", "statement": "The Limma R Package was used to normalize and adjust the the datasets. Differentially expressed genes (DEGs) were screened by LogFC > 2.0 and adj. p value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37173692", "locator": "sections[3] \"Bioinformatics\" paragraph 2", "quote": "The Limma R Package was used to normalize and adjust the the datasets. Differentially expressed genes (DEGs) were screened by LogFC > 2.0 and adj. p value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37173692", "locator": "sections[36] \"notes\" paragraph 1", "quote": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37173692", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73.", "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:37173692"], "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:GSE101920"], "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:GSE101920"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37173692", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-023-04153-z", "sha256": "sha256:5a12340daa7cb69db2d35212a9e6ef5c01c3f22f9ef6076fe0a3ffce656bfb84", "bytes": 47616, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12967-023-04153-z", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10182610", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE101920", "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=GSE101920", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE101920", "version": null, "note": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2718639", "GSM2718640", "GSM2718641", "GSM2718642", "GSM2718643", "GSM2718644", "GSM2718645", "GSM2718646", "GSM2718647", "GSM2718648", "GSM2718649", "GSM2718650", "GSM2718651", "GSM2718652", "GSM2718653", "GSM2718654", "GSM2718655", "GSM2718656", "GSM2718657", "GSM2718658", "GSM2718659", "GSM2718660", "GSM2718661", "GSM2718662"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "16699", "taxon": "Homo sapiens", "title": "Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE31863", "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=GSE31863", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31863", "version": null, "note": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM790257", "GSM790258", "GSM790259", "GSM790260", "GSM790261", "GSM790262", "GSM790263", "GSM790264", "GSM790265", "GSM790266", "GSM790267", "GSM790268", "GSM790269", "GSM790270", "GSM790271", "GSM790272", "GSM790273", "GSM790274", "GSM790275", "GSM790276", "GSM790277", "GSM790278", "GSM790279", "GSM790280", "GSM790281", "GSM790282", "GSM790283", "GSM790284", "GSM790285", "GSM790286", "GSM790287", "GSM790288", "GSM790289", "GSM790290", "GSM790291", "GSM790292", "GSM790293", "GSM790294", "GSM790295", "GSM790296", "GSM790297", "GSM790298", "GSM790299", "GSM790300", "GSM790301", "GSM790302", "GSM790303", "GSM790304", "GSM790305", "GSM790306", "GSM790307", "GSM790308", "GSM790309", "GSM790310", "GSM790311", "GSM790312", "GSM790313", "GSM790314", "GSM790315", "GSM790316", "GSM790317", "GSM790318", "GSM790319", "GSM790320", "GSM790321", "GSM790322", "GSM790323", "GSM790324", "GSM790325", "GSM790326", "GSM790327", "GSM790328", "GSM790329", "GSM790330", "GSM790331", "GSM790332", "GSM790333", "GSM790334", "GSM790335", "GSM790336", "GSM790337", "GSM790338", "GSM790339", "GSM790340", "GSM790341", "GSM790342", "GSM790343", "GSM790344", "GSM790345", "GSM790346", "GSM790347", "GSM790348", "GSM790349", "GSM790350", "GSM790351", "GSM790352", "GSM790353", "GSM790354", "GSM790355", "GSM790356", "GSM790357", "GSM790358", "GSM790359", "GSM790360", "GSM790361", "GSM790362", "GSM790363", "GSM790364", "GSM790365", "GSM790366", "GSM790367", "GSM790368", "GSM790369", "GSM790370", "GSM790371", "GSM790372", "GSM790373", "GSM790374", "GSM790375", "GSM790376", "GSM790377", "GSM790378", "GSM790379", "GSM790380", "GSM790381", "GSM790382", "GSM790383", "GSM790384", "GSM790385", "GSM790386", "GSM790387", "GSM790388", "GSM790389", "GSM790390", "GSM790391", "GSM790392", "GSM790393", "GSM790394", "GSM790395", "GSM790396", "GSM790397", "GSM790398", "GSM790399"], "sample_count": 143, "group_sizes": null, "group_sizes_basis": null, "platform": "14374", "taxon": "Homo sapiens", "title": "Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy.", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE101920 not downloaded", "asset:data:geo:GSE101920 licence not read", "asset:data:geo:GSE31863 not downloaded", "asset:data:geo:GSE31863 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Limma R Package was used to normalize and adjust the the datasets. Differentially expressed genes (DEGs) were screened by LogFC > 2.0 and adj. p value < 0.05."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE31863", "GSE101920"], "resolved_accessions": ["GSE31863", "GSE101920"], "statements": ["All data generated or analysed during this study are included in this article. Additional raw data may be available from the corresponding author for reasonable reasons."], "basis": "The paper names GSE31863, GSE101920 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37173692", "data:geo:GSE101920"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE101920"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:39:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14064, "completion_tokens": 1813, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37173692", "type": "paper", "label": "pmid:37173692"}, {"id": "source:pmid:37173692", "type": "manuscript", "label": "PMID 37173692 full text"}, {"id": "data:geo:GSE101920", "type": "dataset", "label": "GEO GSE101920"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37173692", "type": "paper", "label": "pmid:37173692"}, {"id": "source:pmid:37173692", "type": "manuscript", "label": "PMID 37173692 full text"}, {"id": "data:geo:GSE101920", "type": "dataset", "label": "GEO GSE101920"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37173692", "type": "extraction", "used": ["source:pmid:37173692"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE101920", "type": "accession_resolution", "used": ["data:geo:GSE101920"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37173692", "parent_hash": "sha256:9f707d7da8b21c5a51ab5e40acec919e7103df58b82dbecb2440bea0de426f97", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE101920 licence not read", "asset:data:geo:GSE101920 not downloaded", "asset:data:geo:GSE31863 licence not read", "asset:data:geo:GSE31863 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["31863 and GSE101920. UBE3C overexpression or knockdown was induced in parental or radioresistant BR", "was linked to radioresistance in BRCA. UBE3C knockdown in radioresistant BRCA cells reduced while i", "s was blocked by TP73 overexpression or FOSB knockdown. Additionally, LINC00963 was found to be res"], "order_basis": "paper_text_order:487", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ns were confirmed by immunoprecipitation and immunofluorescence assays. Furthermore, artificial alterations"], "order_basis": "paper_text_order:897", "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": 0.77, "evidence": ["ed the radioresistance of cells in vitro and in vivo. UBE3C, which induced ubiquitination-depende"], "order_basis": "paper_text_order:1294", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["survival (I) of patients in TCGA-BRCA; J, K RT-qPCR and WB analyses for mRNA (J) and protein (K)", "rvival (I) of patients in TCGA-BRCA; J, K RT-qPCR and WB analyses for mRNA (J) and protein (K)"], "order_basis": "paper_text_order:4967", "id": "assay:4"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Limma R Package was used to normalize and adjust the the datasets. Differentially expressed genes (DEGs) were screened by LogFC > 2.0 and adj. p value < 0.05."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}