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pmid:38976072
FERMT1 suppression induces anti-tumor effects and reduces stemness in glioma cancer cells.
Zhigang Pan · Chuhan Ke · Hanlin Zheng · Xiumei Guo · Wen Gao · Xinyue Huang · Chunhui Chen · Yu Xiong · Shuni Zheng · Feng Zheng · Weipeng Hu
Journal of cancer research and clinical oncology · 2024 doi:10.1007/s00432-024-05859-3
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Experiment
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Complete file
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Cancer stem cells (CSCs) have emerged as key contributors to tumor relapse and chemotherapy resistance, making them attractive targets for glioma cancer therapy. This study investigated the potential of FERMT1 as a prognostic biomarker and its role in regulating stemness through cell cycle in glioma.\nMETHODS: Using data from TCGA-GBM, GSE4290, GSE50161 and GSE147352 for analysis of FERMT1 expression in glioma tissues. Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formation ability, invasion and migration were investigated. The influences of FERMT1 on expression of glycolysis-related proteins and levels of ATP, glucose, lactate and G6PDH were also explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced.\nRESULTS: Significant upregulation of FERMT1 in glioma tissues was observed. Silencing FERMT1 not only affected the cell cycle but also led to a notable reduction in proliferation, invasion and migration. The expression of glycolysis-associated proteins including GLUT1, GLUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as well as decreased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover, FERMT1 knockdown significantly reduced sphere diameter, along with inhibiting the expression of transcription factors associated with stemness in glioma cells.\nCONCLUSION: These findings demonstrated that FERMT1 could be an ideal target for the advancement of innovative strategies against glioma treatment via modulating cellular process involved in stemness regulation and metabolism.", "claims": [{"id": "claim-method", "statement": "To determine the significant expression of FERMT1 between normal and glioma samples, we employed the Wilcoxon signed-rank test. 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Additionally, the Kolmogorov-Smirnov test was used to assess the correlation between overall survival probability and FERMT1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used or analyzed during this study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38976072", "locator": "sections[28] \"Data availability\" paragraph 2", "quote": "The datasets used or analyzed during this study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "FERMT1 expression was not significantly associated with patient survival time in the UALCAN analysis (50% cutoff; P = 0.058).", "kind": "quantitative", "target": {"value": 50.0, "unit": "per cent", "tolerance": null, "source": "with a cut off value of 50% and P value = 0.058, there was no significant difference in survival time of patients between high and low FERMT1 expression, the expression level of FERMT1 was not related to the survival time of patients."}, "evidence": [{"asset": "source:pmid:38976072", "locator": "sections[20] \"FERMT1 is a prognostic biomarker for glioma cancer and might be involved in stemness through cell cycle and WNT signaling pathways\" paragraph 2", "quote": "with a cut off value of 50% and P value = 0.058, there was no significant difference in survival time of patients between high and low FERMT1 expression, the expression level of FERMT1 was not related to the survival time of patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "FERMT1 expression was not significantly associated with patient survival time in the UALCAN analysis (50% cutoff; P = 0.058).", "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:38976072"], "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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Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formati", "explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced. RESUL", "LUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as we", "creased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover"], "order_basis": "paper_text_order:640", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["mocell, Xiamen, China), while T98G cells was cultured in MEM medium (Immocell, Xiamen, China). All me"], "order_basis": "paper_text_order:2309", "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": ["Student’s t-test. To quantify the results of Western blotting, we captured and analyzed photographs using"], "order_basis": "paper_text_order:3301", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To determine the significant expression of FERMT1 between normal and glioma samples, we employed the Wilcoxon signed-rank test. Additionally, the Kolmogorov-Smirnov test was used to assess the correlation between overall survival probability and FERMT1."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}