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MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib.


ABSTRACT: Gastrointestinal stromal tumors (GISTs), the most widespread type of sarcoma, contain driver gene mutations predominantly of receptor tyrosine kinase and platelet-derived growth factor receptor alpha. However, the inevitable development of resistance to imatinib (IM) cannot be fully attributed to secondary driver gene mutations. In this study, we investigated the role of microRNA-30a in sensitization of GIST cells to IM in vivo and in vitro. Higher levels of miR-30a were detected in GIST-T1 cells, which were more sensitive to IM than GIST-882 cells. IM treatment also reduced miR-30a levels, indicating the possible role of miR-30a in GIST IM resistance. Subsequently, miR-30a was confirmed to be an IM sensitizer via a mechanism that was attributed to its involvement in the regulation of cell autophagy. The interaction of miR-30a and autophagy in IM treated GIST cells was found to be linked by beclin-1. Beclin-1 knockdown increased IM sensitivity in GIST cell lines. Finally, miR-30a was confirmed to enhance IM sensitivity of GIST cells in mouse tumor models. Our study provides evidence for the possible role of miR-30a in the emergence of secondary IM resistance in GIST patients, indicating a promising target for overcoming this chemoresistance.

SUBMITTER: Chen W 

PROVIDER: S-EPMC7090062 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib.

Chen Wei W   Li Zhouqi Z   Liu Hao H   Jiang Sujing S   Wang Guannan G   Sun Lifeng L   Li Jun J   Wang Xiaochen X   Yu Shaojun S   Huang Jianjin J   Dong Ying Y  

Cell death & disease 20200323 3


Gastrointestinal stromal tumors (GISTs), the most widespread type of sarcoma, contain driver gene mutations predominantly of receptor tyrosine kinase and platelet-derived growth factor receptor alpha. However, the inevitable development of resistance to imatinib (IM) cannot be fully attributed to secondary driver gene mutations. In this study, we investigated the role of microRNA-30a in sensitization of GIST cells to IM in vivo and in vitro. Higher levels of miR-30a were detected in GIST-T1 cell  ...[more]

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