Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells
Abstract We aimed to explore the role of circular RNA 0043256 (circ_0043256) in gastric cancer (GC) and its underlying mechanisms. The impact of circ_0043256 silencing on the proliferation, migration, apoptosis, and aerobic glycolysis of MKN-45 and AGS cells induced by CoCl2 was assessed through the...
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2025-01-01
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author | Wenting Ou Rongjian Tan Jiawei Zhai Lijun Sun Zhenhao Quan Xianjin Huang Feipeng Xu Qingwen Xu Caijin Zhou |
author_facet | Wenting Ou Rongjian Tan Jiawei Zhai Lijun Sun Zhenhao Quan Xianjin Huang Feipeng Xu Qingwen Xu Caijin Zhou |
author_sort | Wenting Ou |
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description | Abstract We aimed to explore the role of circular RNA 0043256 (circ_0043256) in gastric cancer (GC) and its underlying mechanisms. The impact of circ_0043256 silencing on the proliferation, migration, apoptosis, and aerobic glycolysis of MKN-45 and AGS cells induced by CoCl2 was assessed through the utilization of CCK-8, wound healing assay, flow cytometry, and metabolic analysis. The interaction between circ_0043256 and miR-593-5p, as well as the involvement of the miR-593-5p/RRM2 axis in gastric cancer, were confirmed via luciferase assay, Western blot, and bioinformatics analysis. We found that circ_0043256 was up-regulated in GC tissues and CoCl2-treated MKN-45 and AGS cells. Silencing of circ_0043256 reversed CoCl2-induced proliferation, migration, and aerobic glycolysis in MKN-45 and AGS cells. Additionally, circ_0043256 silencing enhanced cell apoptosis and G2/M phase cell cycle arrest in response to CoCl2 treatment. Furthermore, the miR-593-5p/RRM2 axis was identified as a regulatory mechanism for circ_0043256 function in GC. Silencing of circ_0043256 and miR-593-5p mimic co-transfection significantly inhibited CoCl2-induced cellular responses in MKN-45 and AGS cells. A glycolysis inhibitor 2-DG further enhanced the inhibitory effect of circ_0043256 silencing on aerobic glycolysis of CoCl2-induced MKN-45 and AGS cells. Additionally, the inhibition of circ_0043256 resulted in a reduction in tumor volume and the expression of proliferation marker proteins in nude mice. Moreover, the suppression of circ_0043256 led to an increase in miR-593-5p expression and a decrease in RRM2 expression, ultimately causing a decrease in glycolytic-related proteins associated with the glycolytic pathway. Targeting this axis may offer a novel therapeutic approach for treating GC. |
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institution | Kabale University |
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language | English |
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spelling | doaj-art-7632eaa67a8a4e24a942c4811ecada6b2025-01-05T12:17:12ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-84548-0Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cellsWenting Ou0Rongjian Tan1Jiawei Zhai2Lijun Sun3Zhenhao Quan4Xianjin Huang5Feipeng Xu6Qingwen Xu7Caijin Zhou8The Departments of Medical Oncology, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityDepartments of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical UniversityAbstract We aimed to explore the role of circular RNA 0043256 (circ_0043256) in gastric cancer (GC) and its underlying mechanisms. The impact of circ_0043256 silencing on the proliferation, migration, apoptosis, and aerobic glycolysis of MKN-45 and AGS cells induced by CoCl2 was assessed through the utilization of CCK-8, wound healing assay, flow cytometry, and metabolic analysis. The interaction between circ_0043256 and miR-593-5p, as well as the involvement of the miR-593-5p/RRM2 axis in gastric cancer, were confirmed via luciferase assay, Western blot, and bioinformatics analysis. We found that circ_0043256 was up-regulated in GC tissues and CoCl2-treated MKN-45 and AGS cells. Silencing of circ_0043256 reversed CoCl2-induced proliferation, migration, and aerobic glycolysis in MKN-45 and AGS cells. Additionally, circ_0043256 silencing enhanced cell apoptosis and G2/M phase cell cycle arrest in response to CoCl2 treatment. Furthermore, the miR-593-5p/RRM2 axis was identified as a regulatory mechanism for circ_0043256 function in GC. Silencing of circ_0043256 and miR-593-5p mimic co-transfection significantly inhibited CoCl2-induced cellular responses in MKN-45 and AGS cells. A glycolysis inhibitor 2-DG further enhanced the inhibitory effect of circ_0043256 silencing on aerobic glycolysis of CoCl2-induced MKN-45 and AGS cells. Additionally, the inhibition of circ_0043256 resulted in a reduction in tumor volume and the expression of proliferation marker proteins in nude mice. Moreover, the suppression of circ_0043256 led to an increase in miR-593-5p expression and a decrease in RRM2 expression, ultimately causing a decrease in glycolytic-related proteins associated with the glycolytic pathway. Targeting this axis may offer a novel therapeutic approach for treating GC.https://doi.org/10.1038/s41598-024-84548-0Circ_0043256miR-593-5pRRM2Gastric cancerAerobic glycolysis |
spellingShingle | Wenting Ou Rongjian Tan Jiawei Zhai Lijun Sun Zhenhao Quan Xianjin Huang Feipeng Xu Qingwen Xu Caijin Zhou Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells Scientific Reports Circ_0043256 miR-593-5p RRM2 Gastric cancer Aerobic glycolysis |
title | Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells |
title_full | Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells |
title_fullStr | Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells |
title_full_unstemmed | Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells |
title_short | Silencing circ_0043256 inhibited CoCl2-induced proliferation, migration, and aerobic glycolysis in gastric cancer cells |
title_sort | silencing circ 0043256 inhibited cocl2 induced proliferation migration and aerobic glycolysis in gastric cancer cells |
topic | Circ_0043256 miR-593-5p RRM2 Gastric cancer Aerobic glycolysis |
url | https://doi.org/10.1038/s41598-024-84548-0 |
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