Imatinib Regulates miR-483-3p and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors.

Autor: Huang WK; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden.; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan., Shi H; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Akçakaya P; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Zeljic K; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Gangaev A; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Caramuta S; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Yeh CN; Department of Surgery, Chang Gung Memorial Hospital and GIST Team at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan., Bränström R; Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden., Larsson C; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden., Lui WO; Department of Oncology-Pathology, Karolinska Institutet, BioClinicum J6:20, Karolinska University Hospital, 171 64 Solna, Sweden.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Sep 30; Vol. 22 (19). Date of Electronic Publication: 2021 Sep 30.
DOI: 10.3390/ijms221910600
Abstrakt: 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 miR-483-3p 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 miR-483-3p in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that miR-483-3p could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, miR-483-3p overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of miR-483-3p in regulating cell viability upon imatinib treatment.
Databáze: MEDLINE
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