Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29200967", "kind": "science-record", "revision": 7, "content_hash": "sha256:38b8ad133713e3d66b01dc0d06a555c71a3588f25f0bfe4833a298251542c5e9", "created_at": "2026-11-01T15:40:30Z", "updated_at": "2026-11-01T21:59:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.", "doi": "10.1186/s12935-017-0481-z", "pmid": "29200967", "authors": ["Qiong Wang", "Zhongwu Li", "Yaping Wu", "Rong Huang", "Yumin Zhu", "Wei Zhang", "Yanling Wang", "Jie Cheng"], "journal": "Cancer cell international", "year": 2017, "abstract": "BACKGROUND: Bmi1 (B lymphoma Mo-MLV insertion region 1 homolog) contributes to human tumorigenesis via epigenetic transcriptional silencing and represents a novel therapeutic target with great potentials. Here we sought to determine the therapeutic efficiency of PTC-209, a potent and selective Bmi1 inhibitor, in head neck squamous cell carcinoma (HNSCC) cells and a HNSCC xenograft model.\nMETHODS: The mutation pattern, mRNA level of Bmi1 in HNSCC and its associations with clinicopathological parameters were determined through comprehensive data mining and interrogation using publicly available databases GENT, cBioPortal, Oncomine and TCGA. The PTC-209, a selective and potent Bmi1 inhibitor, was exploited and its effect on Bmi1 expression was measured in two HNSCC cell lines Cal27 and FaDu. The phenotypical changes of HNSCC cells were observed upon PTC-209 treatment in vitro. Moreover, the therapeutic effects of PTC-209 for HNSCC were determined in a xenograft animal model.\nRESULTS: Through comprehensive data mining and interrogation, we found that Bmi1 mRNA was frequently overexpressed in a subset of HNSCC samples. Our data revealed that PTC-209 robustly reduced the expression of Bmi1 in Cal27 and FaDu cells presumably by post-transcriptional repression and ubiquitin-proteasomal degradation. PTC-209 treatment resulted in impaired cell proliferation, G1-phase cell cycle arrest, compromised migration and invasiveness, and increased cell apoptosis and chemosensitivity to 5-FU and cisplatin in vitro. Moreover, PTC-209 exposure reduced colony formation, tumorsphere formation and the percentage of ALDH1+ subpopulation in both Cal27 and FaDu cells. Importantly, in vivo PTC-209 administration significantly reduced tumor growth in a HNSCC xenograft model probably by Bmi1 inhibition and impaired cell proliferation.\nCONCLUSIONS: Our findings indicate that pharmacological inhibition of Bmi1 is a novel therapeutic strategy for HNSCC patients, especially with those with aberrant Bmi1 overexpression.", "claims": [{"id": "claim-data-access", "statement": "All original data are available upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29200967", "locator": "sections[25] \"ack\" paragraph 1", "quote": "All original data are available upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Student’s t test or ANOVA with Bonferroni post hoc test, and obtained source data by retrieving Bmi1 mutational and mRNA-expression data from GENT, cBioPortal, Oncomine, and TCGA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29200967", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "All quantitative data in the present study was shown as mean ± SD of two or three independent experiments and compared with Student’s t test or ANOVA with Bonferroni post hoc test unless otherwise specified. p values less than 0.05 (two-sided) were considered statistically significant."}, {"asset": "source:pmid:29200967", "locator": "sections[11] \"Data mining and analysis of Bmi1 in HNSCC via publicly available database\" paragraph 2", "quote": "The original data concerning mutational landscape and expression of Bmi1 mRNA in HNSCC were retrieved from three publicly available databases including GENT (http://medical-genome.kribb.re.kr/GENT/) [28], cBioPortal (http://www.cbioportal.org/) [29], Oncomine (https://www.oncomine.org/) [30] and TCGA (https://cancergenome.nih.gov/)."}, {"asset": "source:pmid:29200967", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through comprehensive data mining and interrogation, we found that Bmi1 mRNA was frequently overexpressed in a subset of HNSCC samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used Student’s t test or ANOVA with Bonferroni post hoc test, and obtained source data by retrieving Bmi1 mutational and mRNA-expression data from GENT, cBioPortal, Oncomine, and TCGA.", "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:29200967"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29200967", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-017-0481-z", "sha256": "sha256:f5ab705737e9398871c4d0a252f72825189ca616d3b564be4e8ec65698f8f1fb", "bytes": 40404, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-017-0481-z", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5697105", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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"}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log-rank"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi square"}}, {"id": "method-4", "family": null, "specific": null, "label": "Student’s t test for Toruner’s cohort and Mann–Whitney U test for Ginos’s cohort; Mann–Whitney U test was also used for the TCGA comparison.", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "reordered", "quote": "“**p < 0.01, Student-t test for Toruner’s data and Mann–Whitney U test for Ginos’s data”"}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All original data are available upon request."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:29200967"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:02Z", "independence": "same_provider"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 78270, "completion_tokens": 5134, "cached_tokens": 2080}}, "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:29200967", "type": "paper", "label": "pmid:29200967"}, {"id": "source:pmid:29200967", "type": "manuscript", "label": "PMID 29200967 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29200967", "type": "paper", "label": "pmid:29200967"}, {"id": "source:pmid:29200967", "type": "manuscript", "label": "PMID 29200967 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29200967", "type": "extraction", "used": ["source:pmid:29200967"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:29200967", "parent_hash": "sha256:8acf4ecbfd17b19f3d4cca672eb2a1b28954d62625357d388693db5e513e37e6", "fork_of": null, "generation": 6}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["gration and invasiveness, and increased cell apoptosis and chemosensitivity to 5-FU and cisplatin i"], "order_basis": "paper_text_order:1519", "id": "assay:1"}, {"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": ["n in both Cal27 and FaDu cells. Importantly, in vivo PTC-209 administration significantly reduced"], "order_basis": "paper_text_order:1743", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ANOVA"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}