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pmid:34790783
COL11A1 promotes esophageal squamous cell carcinoma proliferation and metastasis and is inversely regulated by miR-335-5p.
Zheng Kang · Jiali Zhu · Ning Sun · Xiaomei Zhang · Geyu Liang · Yingying Kou · Huayun Zhu · Cristiano Carbonelli · Yukinori Sakao · Yan Zhang
Annals of translational medicine · 2021 doi:10.21037/atm-21-4951
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Complete file
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This study performed integrated bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE32424, GSE29968, and GSE130078. Collagen type XI alpha 1 (COL11A1) was identified as the hub gene in ESCC progression. The involvement of COL11A1 in ESCC development was next determined using in vitro functional tests.\nMETHODS: Hub genes were identified through integrated bioinformatics analysis. The real-time reverse transcription-polymerase chain reaction was implemented for detecting the expression of COL11A1 mRNA in esophageal cancer cells. KYSE-30 cells were transfected using a vector encoding COL11A1. The proliferation of cells was determined using the Cell Counting Kit-8 (CCK-8) assay. Detection of the cell migration and invasion was made through making use of the transwell test. The development of ESCC cells in vivo was evaluated in naked mice. The interplay among COL11A1 and microRNA-335-5p (miR-335-5p) was discovered using a luciferase reporter experiment.\nRESULTS: In vitro studies showed the upregulation of COL11A1 in ESCC cell lines obtained from ESCC patients and upregulation of COL11A1 was correlated with poor disease-free survival of ESCC patients, thereby implying an oncogenic involvement of COL11A1 in ESCC. Overexpression of COL11A1 enhanced the proliferation of ESCC cells, invasion, and migration; whereas COL11A1 knockdown impeded the proliferation of ESCC cells, invasion, and migration. Additionally, miRNA pathway analysis in combination with TargetScan's online prediction and the luciferase reporter assay suggested miR-335-5p targeting and negatively regulating the COL11A1 3' untranslated region (3'UTR) within ESCC cells. MiR-335-5p overexpression diminished the development of ESCC cells. Additionally, co-expression of COL11A1 ameliorated the repressive influence of miR-335-5p overexpression on the growth and metastasis of ESCC cells.\nCONCLUSIONS: Using comprehensive bioinformatics analysis, the current study identified COL11A1 as an oncogene in ESCC. The mechanistic studies indicated that COL11A1 promoted ESCC cell progression and that miR-335-5p negatively regulated the expression of COL11A1 in ESCC.", "claims": [{"id": "claim-method", "statement": "Survival assessment of the DEGs was executed through making use of the GEPIA database (20) and Kaplan-Meier curves were plotted using data on 364 ESCC patients considering P<0.05 as statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34790783", "locator": "sections[7] \"Hub gene expression level and survival assessment\" paragraph 2", "quote": "Survival assessment of the DEGs was executed through making use of the GEPIA database (20) and Kaplan-Meier curves were plotted using data on 364 ESCC patients considering P<0.05 as statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://dx.doi.org/10.21037/atm-21-4951", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34790783", "locator": "sections[32] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://dx.doi.org/10.21037/atm-21-4951"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Furthermore, the survival analysis revealed that raised COL11A1 expression has an association with shorter disease-free survival in ESCC patients (Figure 3D), implying that COL11A1 plays an oncogenic function in ESCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34790783", "locator": "sections[22] \"Hub gene expression level and survival analysis\" paragraph 2", "quote": "Furthermore, the survival analysis revealed that raised COL11A1 expression has an association with shorter disease-free survival in ESCC patients (Figure 3D), implying that COL11A1 plays an oncogenic function in ESCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Furthermore, the survival analysis revealed that raised COL11A1 expression has an association with shorter disease-free survival in ESCC patients (Figure 3D), implying that COL11A1 plays an oncogenic function in ESCC.", "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:34790783"], "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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