Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10753382 | Biochemical and Biophysical Research Communications | 2014 | 6 Pages |
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.
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Authors
Wei-Zhang Wang, Xiang-Hua Lin, Qiao-Hong Pu, Man-Yu Liu, Li Li, Li-Rong Wu, Qing-Qing Wu, Jian-Wen Mao, Jia-Yong Zhu, Xiao-Bao Jin,