title: 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.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. hayy_lyf@126.com.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D051741:Kruppel-Like Transcription Factors; C062076:zinc finger protein, X-linked; D000068877:Imatinib Mesylate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CML; Imatinib; PI3K/Akt; Proliferation; ZFX