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| Molecular mechanism of withaferin A regulating glycolysis, proliferation, migration and invasion of breast cancer MDA-MB-231 cells through the circOSBPL10/miR-128-3p pathway |
| Hits 482 Download times 417 Received:January 20, 2022 |
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| DOI
10.11656/j.issn.1672-1519.2022.06.24 |
| Key Words
withaferin A;circOSBPL10;miR-128-3p;breast cancer;glycolysis |
| Author Name | Affiliation | | FAN Qian | Department of Breast and Thyroid Surgery, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, China | | YANG Cheng | Department of Breast and Thyroid Surgery, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, China | | LIU Yunshang | Department of Breast and Thyroid Surgery, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, China |
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| Abstract
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| Objective To explore the effect of withaferin A on glycolysis, proliferation, migration and invasion of breast cancer MDA-MB-231 cells and its regulation of circOSBPL10/miR-128-3p pathway.Methods Different concentrations (10, 20, 40 μg/mL) of withaferin A were used to treat breast cancer cells MDA-MB-231 (withaferin A low dose group, withaferin A medium dose group, withaferin A high dose group). si-NC and si-circOSBPL10 were transfected into MDA-MB-231 cells (si-NC group, si-circOSBPL10 group). After pcDNA and pcDNA-circOSBPL10 were transfected into MDA-MB-231 cells respectively, 40 μg/mL withaferin A was added to the cells (bubnerin A+pcDNA group, bubnerin A+pcDNA-circOSBPL10 group). Glucose consumption, lactic acid production and the levels of pyruvate kinase and hexokinase were detected according to the kit. The MTT method was used to detect the inhibition rate of cell proliferation. Transwell chamber experiment was used to detect cell migration and invasion ability. The qRT-PCR method was used to detect the expression of circOSBPL10 and miR-128-3p. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circOSBPL10 and miR-128-3p. Western blot method was used to detect the protein expression of Ki-67, MMP-2 and MMP-9.Results Compared with the control group, glucose consumption, lactate production and the levels of pyruvate kinase and hexokinase in the withaferin A low-dose group, withaferin A medium-dose group, and withaferin A high-dose group were significantly reduced (P < 0.05), and the number of migrating and invasive cells was decreased (P < 0.05), and the protein levels of Ki-67, MMP-2, MMP-9 were decreased (P < 0.05), and the expression level of circOSBPL10 was decreased (P < 0.05), while the cell proliferation inhibition rate was increased (P < 0.05), and the expression level of miR-128-3p was increased (P < 0.05). The dual luciferase reporter gene experiment confirmed that circOSBPL10 could target miR-128-3p. Compared with the si-NC group, glucose consumption, lactate production and the levels of pyruvate kinase and hexokinase in the si-circOSBPL10 group were significantly reduced(P < 0.05), and cell proliferation inhibition rate was increased (P < 0.05), and the number of migration and invasion cells was decreased (P < 0.05), and the protein levels of Ki-67, MMP-2, and MMP-9 were decreased (P < 0.05). Compared with the withaferin A+pcDNA group, the glucose consumption, lactate production and the levels of pyruvate kinase and hexokinase in the withaferin A+pcDNA-circOSBPL10 group were significantly increased (P < 0.05), and the number of migration and invasion cells was increased (P < 0.05), and the protein levels of Ki-67, MMP-2 and MMP-9 were increased (P < 0.05), while the cell proliferation inhibition rate was reduced (P < 0.05).Conclusion withaferin A could inhibit glycolysis, proliferation, migration and invasion of breast cancer cells by regulating the circOSBPL10/miR-128-3p pathway. |
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