1. Targeting miR-21 sensitizes Ph+ ALL Sup-b15 cells to imatinib-induced apoptosis through upregulation of PTEN.
- Author
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Wang, Wei-Zhang, Lin, Xiang-Hua, Pu, Qiao-Hong, Liu, Man-Yu, Li, Li, Wu, Li-Rong, Wu, Qing-Qing, Mao, Jian-Wen, Zhu, Jia-Yong, and Jin, Xiao-Bao
- Subjects
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MICRORNA , *IMATINIB , *APOPTOSIS , *LYMPHOBLASTIC leukemia , *REVERSE transcriptase polymerase chain reaction - Abstract
Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) cells are insensitive to BCR-ABL tyrosine kinase inhibitor imatinib, the underlying mechanisms remain largely unknown. Here, we showed that imatinib treatment induced significant upregulation of miR-21 and downregulation of PTEN in Ph+ ALL cell line Sup-b15. Transient inhibition of miR-21 resulted in increased apoptosis, PTEN upregulation and AKT dephosphorylation, whereas ectopic overexpression of miR-21 further conferred imatinib resistance. Furthermore, knockdown of PTEN protected the cells from imatinib-induced apoptosis achieved by inhibition of miR-21. Additionally, PI3K inhibitors also notably enhanced the effects of imatinib on Sup-b15 cells and primary Ph+ ALL cells similar to miR-21 inhibitor. Therefore, miR-21 contributes to imatinib resistance in Ph+ ALL cells and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to imatinib therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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