Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors
Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the de...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10600 |
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| author | Wen-Kuan Huang Hao Shi Pinar Akçakaya Katarina Zeljic Anastasia Gangaev Stefano Caramuta Chun-Nan Yeh Robert Bränström Catharina Larsson Weng-Onn Lui |
| author_facet | Wen-Kuan Huang Hao Shi Pinar Akçakaya Katarina Zeljic Anastasia Gangaev Stefano Caramuta Chun-Nan Yeh Robert Bränström Catharina Larsson Weng-Onn Lui |
| author_sort | Wen-Kuan Huang |
| collection | DOAJ |
| description | Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that <i>miR-483-3p</i> was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of <i>miR-483-3p</i> in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that <i>miR-483-3p</i> could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, <i>miR-483-3p</i> overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of <i>miR-483-3p</i> in regulating cell viability upon imatinib treatment. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:58:41Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3c6269daa29f4e39a0ccbf66ee48b10f2023-11-22T16:12:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191060010.3390/ijms221910600Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal TumorsWen-Kuan Huang0Hao Shi1Pinar Akçakaya2Katarina Zeljic3Anastasia Gangaev4Stefano Caramuta5Chun-Nan Yeh6Robert Bränström7Catharina Larsson8Weng-Onn Lui9Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Surgery, Chang Gung Memorial Hospital and GIST Team at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, TaiwanDepartment of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, SwedenMetabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that <i>miR-483-3p</i> was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of <i>miR-483-3p</i> in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that <i>miR-483-3p</i> could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, <i>miR-483-3p</i> overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of <i>miR-483-3p</i> in regulating cell viability upon imatinib treatment.https://www.mdpi.com/1422-0067/22/19/10600gastrointestinal stromal tumor (GIST)imatinibmicroRNAoxidative phosphorylation<i>miR-483</i>succinate dehydrogenase B |
| spellingShingle | Wen-Kuan Huang Hao Shi Pinar Akçakaya Katarina Zeljic Anastasia Gangaev Stefano Caramuta Chun-Nan Yeh Robert Bränström Catharina Larsson Weng-Onn Lui Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors International Journal of Molecular Sciences gastrointestinal stromal tumor (GIST) imatinib microRNA oxidative phosphorylation <i>miR-483</i> succinate dehydrogenase B |
| title | Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors |
| title_full | Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors |
| title_fullStr | Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors |
| title_full_unstemmed | Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors |
| title_short | Imatinib Regulates <i>miR-483-3p</i> and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors |
| title_sort | imatinib regulates i mir 483 3p i and mitochondrial respiratory complexes in gastrointestinal stromal tumors |
| topic | gastrointestinal stromal tumor (GIST) imatinib microRNA oxidative phosphorylation <i>miR-483</i> succinate dehydrogenase B |
| url | https://www.mdpi.com/1422-0067/22/19/10600 |
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