Abstract
microRNA profiling of acute myeloid leukemia patient samples identified miR-125a as being decreased. Current literature has investigated miR-125a's role in normal hematopoiesis but not within acute myeloid leukemia. Analysis of the upstream region of miR-125a identified several CpG islands. Both precursor and mature miR-125a increased in response to a de-methylating agent, Decitabine. Profiling revealed the ErbB pathway as significantly decreased with ectopic miR-125a. Either ectopic expression of miR-125a or inhibition of ErbB via Mubritinib resulted in inhibition of cell cycle proliferation and progression with enhanced apoptosis revealing ErbB inhibitors as potential novel therapeutic agents for treating miR-125a-low AML.
Keywords:
Apoptosis; Cell cycle; Methylation; Mubritinib; microRNA-125a.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / pharmacology
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Apoptosis / drug effects
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Azacitidine / analogs & derivatives
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Azacitidine / pharmacology
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Proliferation / drug effects
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CpG Islands / genetics
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Decitabine
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Gene Expression Regulation, Leukemic*
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Hematopoiesis / genetics
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Humans
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myeloid, Acute / metabolism
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Leukemia, Myeloid, Acute / pathology
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Mice
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Mice, Inbred NOD
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Oncogene Proteins v-erbB / antagonists & inhibitors*
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Oncogene Proteins v-erbB / genetics
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Oncogene Proteins v-erbB / metabolism
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Signal Transduction
Substances
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Antimetabolites, Antineoplastic
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MIRN125 microRNA, human
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MicroRNAs
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Oncogene Proteins v-erbB
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Decitabine
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Azacitidine