期刊
CELL DEATH AND DIFFERENTIATION
卷 20, 期 3, 页码 408-418出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2012.130
关键词
hypoxia-inducible factor 1 alpha (HIF-1 alpha); microRNA; acute myeloid leukemia (AML)
资金
- National Key Program (973) for Basic Research of China [2009CB918404]
- National Science Foundation of China [81170505, 81172521, 30971107]
- Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [09SG18]
- Foundation for the author of National Excellent Doctoral Dissertation of China
- Science and Technology Committee of Shanghai [10QA1404000]
Hypoxia-inducible factor 1 (HIF-1) is a crucial transcription factor for the cellular adaptive response to hypoxia, which contributes to multiple events in cancer biology. MicroRNAs (miRNAs) are involved in almost all cellular activities such as differentiation, proliferation, and apoptosis. In this work, we use miRNA microarrays to profile miRNA expression in acute myeloid leukemia (AML) cells with inducible HIF-1 alpha expression, and identify 19 differentially expressed miRNAs. Our study shows that HIF-1 alpha represses the expression of miR-17 and miR-20a by downregulating c-Myc expression. These two miRNAs alleviate hypoxia and HIF-1 alpha-induced differentiation of AML cells. More intriguingly, miR-17 and miR-20a directly inhibit the p21 and STAT3 (signal transducer and activator of transcription 3) expression, both of which can reverse miR-17/miR-20a-mediated abrogation of HIF-1 alpha-induced differentiation. Moreover, we show in vivo that miR-20a contributes to HIF-1 alpha-induced differentiation of leukemic cells. Taken together, our results suggest that HIF-1 alpha regulates the miRNA network to interfere with AML cell differentiation, representing a novel molecular mechanism for HIF-1-mediated anti-leukemic action. Cell Death and Differentiation (2013) 20, 408-418; doi:10.1038/cdd.2012.130; published online 12 October 2012
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