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pmid:38881942
Propofol regulates the progression of hepatocellular carcinoma via the POLR2L/TGF-β signaling pathway.
Jiaying Chen · Jing Xu · Lei Li · Yawei Yuan · Jun Jiang · Yuming Sun
Translational cancer research · 2024 doi:10.21037/tcr-23-2066
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC.\nMethods: The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways.\nResults: Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-β signaling loop.\nConclusions: The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-β signaling pathway.", "claims": [{"id": "claim-method", "statement": "To delve deeper into the complex gene interactions and identify significant modules related to propofol treatment in HCC, we employed the WGCNA methodology.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38881942", "locator": "sections[5] \"Weighted gene co-expression network analysis (WGCNA) of GSE101724 dataset\" paragraph 2", "quote": "To delve deeper into the complex gene interactions and identify significant modules related to propofol treatment in HCC, we employed the WGCNA methodology."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2066/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38881942", "locator": "sections[32] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2066/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38881942", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth.", "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:38881942"], "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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