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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. 454:423-428
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 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.
- Subjects :
- medicine.drug_class
Oligonucleotides
Biophysics
Antineoplastic Agents
Apoptosis
Biochemistry
Tyrosine-kinase inhibitor
Downregulation and upregulation
Cell Line, Tumor
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
medicine
Humans
PTEN
RNA, Small Interfering
Protein Kinase Inhibitors
neoplasms
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Phosphoinositide-3 Kinase Inhibitors
biology
Chemistry
PTEN Phosphohydrolase
Antagomirs
Imatinib
Cell Biology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Molecular biology
Up-Regulation
Gene Expression Regulation, Neoplastic
MicroRNAs
Drug Resistance, Neoplasm
Cell culture
Imatinib Mesylate
Cancer research
biology.protein
RNA Interference
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 454
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....3b0f9db7e2b7f9110aab66a34b1750ad