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Targeting miR-21 sensitizes Ph+ ALL Sup-b15 cells to imatinib-induced apoptosis through upregulation of PTEN.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2014 Nov 21; Vol. 454 (3), pp. 423-8. Date of Electronic Publication: 2014 Oct 27. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Antagomirs
Apoptosis drug effects
Cell Line, Tumor
Gene Expression Regulation, Neoplastic drug effects
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Phosphoinositide-3 Kinase Inhibitors
Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
Protein Kinase Inhibitors pharmacology
RNA Interference
RNA, Small Interfering genetics
Up-Regulation drug effects
Antineoplastic Agents pharmacology
Drug Resistance, Neoplasm drug effects
Imatinib Mesylate pharmacology
MicroRNAs genetics
Oligonucleotides pharmacology
PTEN Phosphohydrolase genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 454
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 25451263
- Full Text :
- https://doi.org/10.1016/j.bbrc.2014.10.107