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

被引:11
作者
Huang, Wen-Kuan [1 ,2 ]
Shi, Hao [1 ]
Akcakaya, Pinar [1 ]
Zeljic, Katarina [1 ]
Gangaev, Anastasia [1 ]
Caramuta, Stefano [1 ]
Yeh, Chun-Nan [3 ,4 ]
Branstrom, Robert [5 ]
Larsson, Catharina [1 ]
Lui, Weng-Onn [1 ]
机构
[1] Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, BioClinicum J6 20, S-17164 Solna, Sweden
[2] Chang Gung Mem Hosp Linkou, Dept Internal Med, Div Hematol Oncol, Taoyuan 33305, Taiwan
[3] Chang Gung Univ, Chang Gung Mem Hosp, Dept Surg, Coll Med, Taoyuan 33305, Taiwan
[4] Chang Gung Univ, GIST Team Linkou, Coll Med, Taoyuan 33305, Taiwan
[5] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden
关键词
gastrointestinal stromal tumor (GIST); imatinib; microRNA; oxidative phosphorylation; miR-483; succinate dehydrogenase B; Complex II; MESSENGER-RNA; EXPRESSION; CANCER; PROLIFERATION; METABOLISM; PROMOTES; EFFICACY; GIST;
D O I
10.3390/ijms221910600
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:12
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