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pmid:39319846
F13B regulates angiogenesis and tumor progression in hepatocellular carcinoma via the HIF-1α/VEGF pathway.
Dong Jiang · Zhi Qi · Zhi-Ying Xu · Yi-Ran Li
Biomolecules & biomedicine · 2024 doi:10.17305/bb.2024.10794
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Experiment
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Complete file
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Through comprehensive bioinformatics analysis of the GSE120123 and The Cancer Genome Atlas (TCGA)-Liver hepatocellular carcinoma (LIHC) datasets, we identified 220 overlapping prognosis-related genes. Eight key genes, including the previously unreported CCDC170 and F13B in HCC, were identified through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis. F13B emerged as a significant prognostic factor in HCC, warranting further investigation in subsequent analyses. In vitro experiments showed that F13B expression was notably reduced in HCC cell lines and tissues, particularly in Huh-7 and SMMC-7721 cells. Overexpression of F13B inhibited cell invasion, migration, and proliferation, while its knockdown produced the opposite effect. A lactate dehydrogenase (LDH) activity assay in human umbilical vein endothelial cells (HUVECs) demonstrated that F13B overexpression reduced vascular endothelial growth factor (VEGF)-induced cytotoxicity, whereas knockdown increased it. Further analysis revealed that F13B negatively regulates VEGFA expression, affecting HUVEC proliferation. In HUVECs, F13B overexpression reversed VEGF-induced upregulation of key angiogenesis markers, including phospho-VEGF receptor 2 (p-VEGFR2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), as well as AKT/mTOR signaling proteins, phospho-Akt (p-AKT), and phospho-mTOR (p-mTOR). Additionally, F13B negatively regulated VEGFA and hypoxia-inducible factor 1 A (HIF1A) under hypoxic conditions, counteracting the hypoxia-induced increase in cell viability. These findings suggest that F13B regulates angiogenesis through the HIF-1α/VEGF pathway and plays a crucial role in HCC progression. Our results highlight the potential of F13B as a therapeutic target in HCC, providing novel insights into the molecular mechanisms of HCC and its prognostic significance.", "claims": [{"id": "claim-method", "statement": "LASSO-Cox regression analysis was performed on the 57 genes with significant P values. Through ten-fold cross-validation, we identified eight key genes with λmin ═ 0.0429 (Figure S3A and S3B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39319846", "locator": "sections[24] \"LASSO-Cox regression analysis and prognostic model validation\" paragraph 2", "quote": "LASSO-Cox regression analysis was performed on the 57 genes with significant P values. Through ten-fold cross-validation, we identified eight key genes with λmin ═ 0.0429 (Figure S3A and S3B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39319846", "locator": "sections[38] \"Data Availability\" paragraph 2", "quote": "The datasets used and/or analyzed during the study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "F13B expression was independently associated with overall survival in HCC (P ═ 0.03429, HR ═ 0.90504, 95% CI: 0.82517–0.99264).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Multivariate analysis confirmed that F13B was an independent prognostic factor for OS (P ═ 0.03429, HR ═ 0.90504, 95% CI: 0.82517–0.99264) (Figure 3B)."}, "evidence": [{"asset": "source:pmid:39319846", "locator": "sections[26] \"Prognostic validation of F13B and nomogram construction for survival prediction\" paragraph 2", "quote": "Multivariate analysis confirmed that F13B was an independent prognostic factor for OS (P ═ 0.03429, HR ═ 0.90504, 95% CI: 0.82517–0.99264) (Figure 3B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "F13B expression was independently associated with overall survival in HCC (P ═ 0.03429, HR ═ 0.90504, 95% CI: 0.82517–0.99264).", "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:39319846"], "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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