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pmid:38493179
Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.
Shihao Hong · Ni Fu · Shanliang Sang · Xudong Ma · Fangying Sun · Xiao Zhang
Journal of ovarian research · 2024 doi:10.1186/s13048-024-01386-4
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Experiment
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Complete file
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The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes.\nMETHODS: The present study used the differentially expressed genes (DEGs) obtained from the \"Limma\" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity.\nRESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion.\nCONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.", "claims": [{"id": "claim-method", "statement": "Differential gene analysis was performed on GSE66957 using the “Limma” package, with |logFC|> 1 and a p-value < 0.05 indicating significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38493179", "locator": "sections[4] \"Identification of differentially expressed genes with Limma\" paragraph 2", "quote": "Differential gene analysis was performed on GSE66957 using the “Limma” package, with |logFC|> 1 and a p-value < 0.05 indicating significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38493179", "locator": "sections[35] \"Availability of data and materials\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38493179", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases.", "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:38493179"], "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. 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RT-qPCR and IHC confirmed the RNA and protein levels", "rther confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels"], "order_basis": "paper_text_order:940", "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": 0.85, "evidence": ["firmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6"], "order_basis": "paper_text_order:951", "id": "assay:2"}, {"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": ["Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migratio", "Methods Cell culture and transfection The human OC cell line SKOV3 (Homo sapiens,", "V3 cells were cultured in 12-well plates and transfected with si-NC or si-IRF6 using Lipofectamine 30", "sing mycoplasma-free cells. The sequences of siRNA-IRF6 and si-control were 5ʹ- CTGAGCATATTACCA"], "order_basis": "paper_text_order:1458", "id": "assay:3"}, {"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": ["thenticated by STR profiling. The cells were cultured in DMEM supplemented with 10% FBS, 100 U/mL of", "bated at 37 °C with 5% CO2. SKOV3 cells were cultured in 12-well plates and transfected with si-NC or"], "order_basis": "paper_text_order:1943", "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": ["Differential gene analysis was performed on GSE66957 using the “Limma” package, with |logFC|> 1 and a p-value < 0.05 indicating significance."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}