Abstract
Zinc finger protein, X-linked (ZFX) mediates the development and progression of human cancers. However, its potential role in chronic myeloid leukemia (CML) is still unknown. The ZFX expression was significantly increased in CML patients and cell lines. Based on loss-of-function experiments in CML cells, we found that knockdown of ZFX expression impaired cell proliferation and induced mitotic arrest in G0/G1 stage and apoptosis. In addition, ZFX silencing sensitized CML cells to imatinib treatment. Further, phospho-Akt (p-Akt), CyclinD1, CyclinE1, and Bcl-2 were downregulated, and Caspase-3 was upregulated in ZFX-silenced cells. In summary, our data suggest that ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway. ZFX may represent a potential therapeutic target in CML.
Keywords:
CML; Imatinib; PI3K/Akt; Proliferation; ZFX.
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics
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Bone Marrow / drug effects
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Bone Marrow / metabolism
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / genetics
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Cell Proliferation / drug effects
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Cell Proliferation / genetics
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Drug Resistance, Neoplasm* / genetics
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Humans
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Imatinib Mesylate / pharmacology*
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Imatinib Mesylate / therapeutic use
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K562 Cells
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Kruppel-Like Transcription Factors / deficiency
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
Substances
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Kruppel-Like Transcription Factors
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zinc finger protein, X-linked
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Imatinib Mesylate
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt