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pmid:38021159
APOBEC3A suppresses cervical cancer via apoptosis.
Zishuai Li · Haiwei He · Xiangyu Ren · Yifan Chen · Wenbin Liu · Rui Pu · Letian Fang · Yiwei Shi · Donghong Liu · Jiayi Zhao · Zheyun Niu · Mingjuan Xu · Guangwen Cao
Journal of Cancer · 2023 doi:10.7150/jca.89044
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Experiment
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Data
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Analysis
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Complete file
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However, the role of APOBEC3A in cervical cancer remains to be clarified. Methods: We used bioinformatics to investigate APOBEC3A expression and outcomes using The Cancer Genome Atlas (TCGA)-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) dataset, GTEx, and GSE7803. Immunohistochemistry was then used to identify APOBEC3A's expression pattern. We performed Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays to measure proliferation, migration, invasion, and apoptosis, respectively, using the SiHa and HeLa cell lines transfected with APOBEC3A. BALB/c nude mice were used to investigate the effects of APOBEC3A in vivo. The phosphorylated gamma-H2AX staining assay was applied to measure DNA damage. RNA sequencing (RNA-Seq) was applied to explore APOBEC3A-related signaling pathways. Results: APOBEC3A was more significantly expressed in cancer tissues than in adjacent normal tissues. Higher expression of APOBEC3A was associated with better outcomes in TCGA-CESC and GTEx. Immunohistochemistry showed that the expression of APOBEC3A was significantly higher in cancer tissues than in normal tissues. Transfection experiments showed that APOBEC3A inhibited proliferation, upregulated S-phase cells, inhibited migration and invasion, induced DNA damage, and promoted apoptosis. Overexpression of APOBEC3A inhibited tumor formation in the mouse model. RNA-seq analysis showed that ectopic expression of APOBEC3A inhibited several cancer-associated signaling pathways. Conclusions: APOBEC3A is significantly upregulated in cervical cancer, and higher expression of APOBEC3A is associated with better outcomes. APOBEC3A is a tumor suppressor whose overexpression induces apoptosis in cervical cancer.", "claims": [{"id": "claim-method", "statement": "The Student's t-test was used to determine differences in continuous variables, while the chi-square test was used to evaluate differences in categorical variables.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38021159", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "The Student's t-test was used to determine differences in continuous variables, while the chi-square test was used to evaluate differences in categorical variables."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38021159", "locator": "sections[23] \"Availability of data and materials\" paragraph 2", "quote": "The raw data are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "APOBEC3A and UNG expression levels were significantly higher in cervical cancer than in adjacent normal tissues, according to TCGA and GTEx (P < 0.001, Figures 1A and B).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "APOBEC3A and UNG expression levels were significantly higher in cervical cancer than in adjacent normal tissues, according to TCGA and GTEx (P < 0.001, Figures 1A and B)."}, "evidence": [{"asset": "source:pmid:38021159", "locator": "sections[15] \"APOBEC3A is significantly upregulated in cervical cancer, and higher expression of APOBEC3A is associated with better outcomes\" paragraph 2", "quote": "APOBEC3A and UNG expression levels were significantly higher in cervical cancer than in adjacent normal tissues, according to TCGA and GTEx (P < 0.001, Figures 1A and B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "APOBEC3A and UNG expression levels were significantly higher in cervical cancer than in adjacent normal tissues, according to TCGA and GTEx (P < 0.001, Figures 1A and B).", "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:38021159"], "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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