Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells

Y. Yu, L. Yang, M. Zhao, S. Zhu, R. Kang, P. Vernon, D. Tang, L. Cao

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

A major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib and other BCR-ABL tyrosine kinase inhibitors. MicroRNAs (miRNAs) are small RNA molecules that influence gene expression by post-transcriptional regulation of messenger RNA. It is not yet clear how miRNAs are able to regulate the effectiveness of imatinib in CML. Here, we show that imatinib markedly inhibits expression of miR-30a in human CML cells. miR-30a is a potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. miR-30a mimic or knockdown of autophagy genes (ATGs) such as Beclin 1 and ATG5 by short hairpin RNA enhances imatinib-induced cytotoxicity and promotes mitochondria-dependent intrinsic apoptosis. In contrast, knockdown of miR-30a by antagomir-30a increases the expression of Beclin 1 and ATG5, and inhibits imatinib-induced cytotoxicity. These findings indicate that dysregulation of miR-30a may interfere with the effectiveness of imatinib-mediated apoptosis by an autophagy-dependent pathway, thus representing a novel potential therapeutic target in CML.

Original languageEnglish (US)
Pages (from-to)1752-1760
Number of pages9
JournalLeukemia
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

Autophagy
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
MicroRNAs
Human Activities
Apoptosis
Gene Knockdown Techniques
Protein-Tyrosine Kinases
Small Interfering RNA
Imatinib Mesylate
Mitochondria
Down-Regulation
RNA
Gene Expression
Messenger RNA
Beclin-1

Keywords

  • autophagy
  • chronic myeloid leukemia
  • imatinib
  • microRNA
  • stem cell

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. / Yu, Y.; Yang, L.; Zhao, M.; Zhu, S.; Kang, R.; Vernon, P.; Tang, D.; Cao, L.

In: Leukemia, Vol. 26, No. 8, 01.08.2012, p. 1752-1760.

Research output: Contribution to journalArticle

Yu, Y. ; Yang, L. ; Zhao, M. ; Zhu, S. ; Kang, R. ; Vernon, P. ; Tang, D. ; Cao, L. / Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. In: Leukemia. 2012 ; Vol. 26, No. 8. pp. 1752-1760.
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