Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis
Imatinib is a classical targeted drug to treat chronic myeloid leukemia (CML). However, it shows cardiotoxicity, which limits its clinical application. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) shows proapoptotic properties in human cells. This study is performed to investigate...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2023/1108280 |
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| author | Peng Tang Jinjian Zhou Huagang Liu Shenglan Mei Kai Wang Hao Ming |
| author_facet | Peng Tang Jinjian Zhou Huagang Liu Shenglan Mei Kai Wang Hao Ming |
| author_sort | Peng Tang |
| collection | DOAJ |
| description | Imatinib is a classical targeted drug to treat chronic myeloid leukemia (CML). However, it shows cardiotoxicity, which limits its clinical application. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) shows proapoptotic properties in human cells. This study is performed to investigate whether targeting MEG3 can attenuate imatinib-mediated cardiotoxicity to cardiomyocytes. In this work, H9c2 cells were divided into four groups: control group, hypoxia group, hypoxia + imatinib, and hypoxia + imatinib + MEG3 knockdown group. MEG3 and microRNA-129-5p (miR-129-5p) expression levels were detected by the quantitative real-time PCR (qRT-PCR). The viability and apoptosis of H9c2 cells were then evaluated by cell counting kit-8 (CCK-8), flow cytometry, and TUNEL assays. The targeting relationships between MEG3 and miR-129-5p, between miR-129-5p and high-mobility group box 1 (HMBG1), were validated by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. The protein expression level of HMGB1 was detected by western blot. It was revealed that, Imatinib-inhibited cell viability and aggravated the apoptosis of H9c2 cells cultured in hypoxic condition, and MEG3 knockdown significantly counteracted this effect. MiR-129-5p was a downstream target of MEG3 and it directly targeted HMGB1, and knockdown of MEG3 inhibited HMGB1 expression in H9c2 cells. In conclusion, targeting MEG3 ameliorates imatinib-induced injury of cardiomyocytes via regulating miR-129-5p/HMGB1 axis. |
| format | Article |
| id | doaj-art-3f4223bad651428e894970e85ecda8df |
| institution | OA Journals |
| issn | 2210-7185 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-3f4223bad651428e894970e85ecda8df2025-08-20T02:08:07ZengWileyAnalytical Cellular Pathology2210-71852023-01-01202310.1155/2023/1108280Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 AxisPeng Tang0Jinjian Zhou1Huagang Liu2Shenglan Mei3Kai Wang4Hao Ming5Department of Vascular SurgeryDepartment of AnesthesiologyDepartment of Vascular SurgeryDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyImatinib is a classical targeted drug to treat chronic myeloid leukemia (CML). However, it shows cardiotoxicity, which limits its clinical application. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) shows proapoptotic properties in human cells. This study is performed to investigate whether targeting MEG3 can attenuate imatinib-mediated cardiotoxicity to cardiomyocytes. In this work, H9c2 cells were divided into four groups: control group, hypoxia group, hypoxia + imatinib, and hypoxia + imatinib + MEG3 knockdown group. MEG3 and microRNA-129-5p (miR-129-5p) expression levels were detected by the quantitative real-time PCR (qRT-PCR). The viability and apoptosis of H9c2 cells were then evaluated by cell counting kit-8 (CCK-8), flow cytometry, and TUNEL assays. The targeting relationships between MEG3 and miR-129-5p, between miR-129-5p and high-mobility group box 1 (HMBG1), were validated by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. The protein expression level of HMGB1 was detected by western blot. It was revealed that, Imatinib-inhibited cell viability and aggravated the apoptosis of H9c2 cells cultured in hypoxic condition, and MEG3 knockdown significantly counteracted this effect. MiR-129-5p was a downstream target of MEG3 and it directly targeted HMGB1, and knockdown of MEG3 inhibited HMGB1 expression in H9c2 cells. In conclusion, targeting MEG3 ameliorates imatinib-induced injury of cardiomyocytes via regulating miR-129-5p/HMGB1 axis.http://dx.doi.org/10.1155/2023/1108280 |
| spellingShingle | Peng Tang Jinjian Zhou Huagang Liu Shenglan Mei Kai Wang Hao Ming Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis Analytical Cellular Pathology |
| title | Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis |
| title_full | Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis |
| title_fullStr | Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis |
| title_full_unstemmed | Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis |
| title_short | Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis |
| title_sort | depletion of lncrna meg3 ameliorates imatinib induced injury of cardiomyocytes via regulating mir 129 5p hmgb1 axis |
| url | http://dx.doi.org/10.1155/2023/1108280 |
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