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pmid:30349307
MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial-mesenchymal transition in lung cancer cells.
Bo Pan · Haibo Han · Lina Wu · Ying Xiong · Jianzhi Zhang · Bin Dong · Yue Yang · Jinfeng Chen
OncoTargets and therapy · 2018 doi:10.2147/OTT.S167963
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Experiment
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Complete file
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Partek Genomics Suite software was used to identify survival-related genes for finding candidate indicators for early-stage patients at risk of recurrence. Differential expression of MTBP (MDM2 binding protein) in early-stage lung adenocarcinoma tissues was determined by immunohistochemical staining. The effects of MTBP interference expression and overexpression on viability, migration, and invasion capacity of lung cells were evaluated using Cell Counting Kit-8, wound healing, and Transwell assays. The tumor growth and lung metastasis in vivo were observed in chick embryo chorioallantoic membrane model. Human Exon 2.0 ST Array was used to analyze downstream regulation genes of MTBP in lung cancer cells. Involvement of ZEB2 and epithelial-mesenchymal transition (EMT) markers was investigated by Western blot.\nRESULTS: By mining GEO database, we identified MTBP as a poor prognostic indicator of stage I lung adenocarcinomas. In addition, increased expression of MTBP was also associated with poor survival in our early-stage lung adenocarcinoma cohort. Further experiment suggested that knockdown of MTBP suppressed the migration and invasion of A549 and H1975 cells in vitro and in vivo, whereas overexpression of MTBP in HCC827 and PC9 cells promoted the migration and invasion in vitro and in vivo. Furthermore, ZEB2 upregulation directly activated EMT to mediate the downstream effects of MTBP involved in lung cancer cells metastasis.\nCONCLUSION: MTBP is an independent indicator for poor prognosis in stage I lung adenocarcinomas and might promote the aggressive phenotype of non-small-cell lung cancer by inducing the EMT process through upregulating ZEB2 expression.", "claims": [{"id": "claim-method", "statement": "Cox proportional hazard model was built in order to identify the potential risk factors associated with prognosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30349307", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Cox proportional hazard model was built in order to identify the potential risk factors associated with prognosis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile and related clinical pathological information of stage I lung adenocarcinoma in four gene series, including GSE50081, GSE30219, GSE37745, and GSE13213, were extracted from GEO (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30349307", "locator": "sections[3] \"Mining GEO database\" paragraph 2", "quote": "The gene expression profile and related clinical pathological information of stage I lung adenocarcinoma in four gene series, including GSE50081, GSE30219, GSE37745, and GSE13213, were extracted from GEO (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:30349307"], "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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"section_title": "Supplementary materials", "row_count": 32, "column_count": 4}, "table": {"label": "Table S3", "caption": "Eighty candidate downstream genes of MTBP identified by Venn diagram analysis of consistent DEGs in different cells with knockdown or overexpression of MTBP cells", "rows": [["Protein coding", "microRNA", "Noncoding RNA", "Pseudogene"], [""], ["ZNF480", "MIR579", "LINC01166", "RPL23AP64"], ["ZNF443", "MIR548T", "OLMALINC", "ZSCAN5CP"], ["ZNF430", "MIR548K", "FAM182A", "TMEM14EP"], ["ZEB2", "MIR548J", "DIP2A-IT1", "LPAL2"], ["ZCWPW2", "MIR548A2", "AGAP1-IT1", "INGX"], ["WDR7", "MIR520F", "SNORD90", "LOC441455"], ["UBC", "MIR520E", "SNORD20", ""], ["TRIM64B", "MIR513A1", "SNORD116-11", ""], ["TRBV7-4", "MIR505", "SNORD111", ""], ["TRAV8-3", "MIR4802", "LOC105377384", ""], ["TNFSF18", "MIR4679-2", "LOC105377276", ""], ["TMEM241", "MIR4655", "LOC105374838", ""], ["SPANXC", "MIR4451", "LOC105372571", ""], ["SMR3A", "MIR4261", "LOC105369595", ""], ["SMIM22", "MIR3908", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE50081", "GSE30219", "GSE37745", "GSE13213"], "resolved_accessions": ["GSE50081", "GSE30219", "GSE37745", "GSE13213"], "statements": ["The gene expression profile and related clinical pathological information of stage I lung adenocarcinoma in four gene series, including GSE50081, GSE30219, GSE37745, and GSE13213, were extracted from GEO (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE50081, GSE30219, GSE37745, GSE13213 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:30349307", "data:geo:GSE13213", "asset:table:pmid:30349307:1", "asset:table:pmid:30349307:2", "asset:table:pmid:30349307:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13213"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:12:39Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 30371, "completion_tokens": 1216, "cached_tokens": 784}}, "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:30349307", "type": "paper", "label": "pmid:30349307"}, {"id": "source:pmid:30349307", "type": "manuscript", "label": "PMID 30349307 full text"}, {"id": "data:geo:GSE13213", "type": "dataset", "label": "GEO GSE13213"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30349307", "type": "paper", "label": "pmid:30349307"}, {"id": "source:pmid:30349307", "type": "manuscript", "label": "PMID 30349307 full text"}, {"id": "data:geo:GSE13213", "type": "dataset", "label": "GEO GSE13213"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30349307", "type": "extraction", "used": ["source:pmid:30349307"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13213", "type": "accession_resolution", "used": ["data:geo:GSE13213"], "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:30349307", "parent_hash": "sha256:b11c7cbe2d0fedd32c9f0ef3495e24cb9cc16b532d5cf29c28ee9afa9c1631eb", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE13213 licence not read", "asset:data:geo:GSE13213 not downloaded", "asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE30219 not downloaded", "asset:data:geo:GSE37745 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE50081 licence not read", "asset:data:geo:GSE50081 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["ung adenocarcinoma tissues was determined by immunohistochemical staining. The effects of MTBP interference e"], "order_basis": "paper_text_order:702", "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": 0.99, "evidence": ["assays. The tumor growth and lung metastasis in vivo were observed in chick embryo chorioallantoi", "nvasion of A549 and H1975 cells in vitro and in vivo, whereas overexpression of MTBP in HCC827 an", "oted the migration and invasion in vitro and in vivo. Furthermore, ZEB2 upregulation directly act"], "order_basis": "paper_text_order:972", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["transition (EMT) markers was investigated by Western blot. RESULTS: By mining GEO database, we identif"], "order_basis": "paper_text_order:1236", "id": "assay:3"}, {"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": ["ma cohort. Further experiment suggested that knockdown of MTBP suppressed the migration and invasio", ". (C) Cell viability of A549 and H1975 cells transfected with MTBP shRNA lentiviruses and scramble le", "s of consistent DEGs in different cells with knockdown or overexpression of MTBP cellsProtein codin", "f A549 and H1975 cells transfected with MTBP shRNA lentiviruses and scramble lentiviruses was d"], "order_basis": "paper_text_order:1528", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["TBP suppressed the migration and invasion of A549 and H1975 cells in vitro and in vivo, wherea", "g Union Medical College (Beijing, China) and cultured in RPMI-1640 medium, with 10% FBS, 100 U/mL pen", "ions. Cell culture All cell lines, including A549, H1299, H1650, H1975, HCC827, and PC9, were", "dependent experiments. (C) Cell viability of A549 and H1975 cells transfected with MTBP shRNA"], "order_basis": "paper_text_order:1587", "id": "assay:5"}, {"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": ["easured in lung adenocarcinoma cell lines by qPCR. Data represent the mean ± SD of results fro", "MDM2 binding protein; OS, overall survival; qPCR, quantitative PCR. Table S1Clinical characte"], "order_basis": "paper_text_order:4495", "id": "assay:6"}, {"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": ["and scramble lentiviruses was determined by CCK-8 assays (two-way ANOVA, P>0.05).Abbreviations", "ssays (two-way ANOVA, P>0.05).Abbreviations: CCK-8, Cell Counting Kit-8; MTBP, MDM2 binding pro"], "order_basis": "paper_text_order:4706", "id": "assay:7"}, {"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:8"}]}