ZFX Facilitates Cell Proliferation and Imatinib Resistance in Chronic Myeloid Leukemia Cells.

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.

• Authors: Jingjing Wu, Bin Wei, Qian Wang, Yihan Ding, Zhikui Deng, Xueying Lu, Yufeng Li
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 74 Issue 2 Pg. 277-83 (Jun 2016) ISSN: 1559-0283 [Electronic] United States
• PMID: 26912059 (Publication Type: Journal Article)

Chemical References

• Kruppel-Like Transcription Factors
• zinc finger protein, X-linked
• Imatinib Mesylate
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis (drug effects, genetics)
• Bone Marrow (drug effects, metabolism)
• Cell Cycle Checkpoints (drug effects, genetics)
• Cell Proliferation (drug effects, genetics)
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Imatinib Mesylate (pharmacology, therapeutic use)
• K562 Cells
• Kruppel-Like Transcription Factors (deficiency, genetics, metabolism)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects, genetics)