GATA4 is highly expressed in childhood acute lymphoblastic leukemia, promotes cell proliferation and inhibits apoptosis by activating BCL2 and MDM2

GATA4 在儿童急性淋巴细胞白血病中高表达,通过激活 BCL2 和 MDM2 促进细胞增殖并抑制细胞凋亡

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作者:Qiuguo Han, Xin Xu, Jing Li, Jinggang Wang, Li Bai, Aihong Wang, Wei Wang, Bo Zhang

Abstract

Members of the GATA‑binding factor protein family, including GATA1, GATA2 and GATA3, serve an inhibiting role in leukemia. The present study demonstrated that GATA4 was upregulated in children with acute lymphoblastic leukemia (ALL). Results from a number of functional experiments, including cell proliferation analysis, cell cycle analysis, cell apoptosis assay and Transwell migration and invasion analyses, have suggested that high expression of GATA4 may facilitate proliferation and metastasis, and suppress apoptosis in ALL cells. Chromatin immunoprecipitation assay and luciferase reporter assay revealed that GATA4 was a transcription factor that activated mouse double minute 2 homolog (MDM2) and B cell lymphoma 2 (BCL2) expression in ALL cells. BCL2 is a key anti‑apoptosis protein that was demonstrated to suppress cell apoptosis. In addition, GATA4 was revealed to regulate p53 through the transcriptional activation of MDM2, subsequently influencing cell cycle and apoptosis. Results from the present study suggested that GATA4 may be a key marker in ALL diagnosis and a potential target of molecular therapy.

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