Comprehensive analysis of circular RNA-associated competing endogenous RNA networks and immune infiltration in gastric cancer |
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| Affiliation: | 1. Department of Gastroenterology, The Third Affiliated Hospital of Shanghai University, Wenzhou People''s Hospital, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou 325000, Zhejiang, China;2. Soochow University, Suzhou 215000, Jiangsu, China;3. Department of Gastroenterology, Zhejiang Provincial People''s Hospital, Hangzhou 310000, Zhejiang, China;4. Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People''s Hospital, Wenzhou 325000, Zhejiang, China;5. Zhejiang University of Technology, Hangzhou 310000, Zhejiang, China;1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Anatomical Sciences, Sarab Faculty of Medical Sciences, Sarab, Iran;3. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;4. Medical and molecular genetics, Ataturk University, Erzurum, Turkey;5. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;6. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of General, Visceral, and Transplant Surgery, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;2. Walter-Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;3. Institute of Laboratory Medicine, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;1. Department of Neurology, Guangzhou First People''s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China;2. Department of Neurology, Guangzhou First People''s Hospital, Guangzhou Medical University, Guangzhou 510180, China;3. Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510180, China;1. The First People''s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China;2. Department of General Surgery, Wujin Affiliated Hospital of Jiangsu University and The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China;3. Department of Gastrointestinal Sugery, The First People''s Hospital of Changzhou, The Third Affiliated Hospital of Soohow University, Changzhou, Jiangsu, China;2. Department of Thoracic and Cardiovascular Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Republic of Korea;3. Department of Thoracic and Cardiovascular Surgery, Ajou University Hospital, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea |
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| Abstract: | BackgroundCircular RNA (circRNA) has been proved to be an important regulator of gastric cancer (GC). However, the role and regulatory mechanism of circrna related competitive endogenous RNA (ceRNA) in GC have not been established.MethodsCircRNA data and clinical data were obtained from the GEO and TCGA databases. The ceRNA networks were constructed and a function enrichment analysis was completed. Additionally, correlations between hub genes expression, immune cell infiltration, and clinical phenotypes were determined. The differentially expressed circRNAs and their downstream microRNAs (miRNAs) were validated by quantitative real-time polymerase chain reaction, and the hub genes were validated by western blot analysis. The migration and invasion ability of overexpressed hsa_circ_0002504 was determined by a transwell assay.ResultsThe ceRNA network contained 2 circRNAs, 3 miRNAs, and 55 messenger RNAs (mRNAs). 323 biological processes terms, 53 cellular components terms, 51 molecular functions terms, and 4 signaling pathways were revealed by the function enrichment analysis. The GSEA analysis revealed that the hub genes were positively correlated with the axon guidance and adhesion molecules pathways. The correlation analysis revealed that overexpressed EPHA4 and KCNA1 indicated poor tissue differentiation and were associated with clinically advanced stages of GC. The in vitro experiments showed that hsa_circ_0002504 was significantly down-regulated in GC cell lines. In addition, the overexpression of hsa_circ_0002504 led to a significant downregulation of hsa-miR-615-5p and hsa-miR-767-5p, as well as an upregulation of EPHA4, KCNA1, and NCAM1. Furthermore, it suppressed the migration and invasion ability of GC cells.ConclusionsHsa_circ_0002504 is a potential diagnostic biomarker for GC. High expression of EPHA4 and KCNA1 may indicate poor prognosis. |
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