microRNA 30A promotes autophagy in response to cancer therapy

Yan Yu, Lizhi Cao, Liangchun Yang, Rui Kang, Michael Lotze, Daolin Tang

Research output: Contribution to journalShort survey

59 Scopus citations

Abstract

microRNAs (miRNAs) are a class of small regulatory RNAs that regulate gene expression at the post-transcriptional level. miRNAs play important roles in the regulation of development, growth, and metastasis of cancer, and in determining the response of tumor cells to anticancer therapy. In recent years, they have also emerged as important regulators of autophagy, a lysosomal-mediated pathway that contributes to degradation of a cell's own components. Imatinib, a targeted competitive inhibitor of the BCR-ABL1 tyrosine kinase, has revolutionized the clinical treatment of chronic myelogenous leukemia (CML). We demonstrate that MIR30A-mediated autophagy enhances imatinib resistance against CML including primary stem and progenitor cells. MIR30A, but not MIR101, is a potent inhibitor of autophagy by selectively downregulating BECN1 and ATG5 expression in CML cells. MIR30A mimics, as well as knockdown of BECN1 and ATG5, increases intrinsic apoptotic pathways. In contrast, the antagomir-30A increases autophagy and inhibits intrinsic apoptotic pathways, confirming that autophagy serves to protect against apoptosis. Taken together, these data clarify some of the underlying molecular mechanisms of tyrosine kinase inhibitor-induced autophagy.

Original languageEnglish (US)
Pages (from-to)853-855
Number of pages3
JournalAutophagy
Volume8
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Keywords

  • Atg5
  • Autophagy
  • BCR-ABL tyrosine kinase
  • Beclin 1
  • Chronic myelogenous leukemia
  • microRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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