ZFX modulates the growth of human leukemic cells via B4GALT1
ZFX modulates the growth of human leukemic cells via B4GALT1
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ZFX 通过 B4GALT1 调节人类白血病细胞的生长
DOI：
10.1093/abbs/gmw109
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发表时间：
2016-12-01
影响因子：
3.7
通讯作者：
Zhang，Xiuyan
中科院分区：
文献类型：
--
作者：
Wu，Jie;Xiao，Lun;Zhang，Xiuyan
锌指蛋白X连锁（ZFX）是胚胎干细胞（ESC）和造血干细胞（HSC）的关键调节因子，其是小鼠模型中Notch胞内结构域（NotchIC）诱导的急性T细胞白血病和MLL-AF 9诱导的髓样白血病所需的。然而，ZFX在人类白血病细胞中的作用及其潜在机制尚不清楚，尽管越来越多的数据表明ZFX在各种人类肿瘤中异常表达并发挥重要作用。在此，我们发现ZFX在各种人白血病细胞系和白血病患者的原代细胞中与对照细胞相比有异常表达。ZFX的沉默通过细胞周期失调或诱导包括K562、Jurkat、Namalwa和THP-1细胞在内的各种细胞的凋亡而导致生长抑制。基因表达分析显示，在ZFX沉默后，UDP-Gal：βGlcNAc β 1，4-半乳糖基转移酶，多肽1（B4 GALT 1）显著下调，这与K562细胞对甲磺酸伊马替尼（IM）处理的反应有关。此外，凝集素印迹分析表明，在K562细胞中的糖蛋白的半乳糖基化被抑制ZFX沉默后。有趣的是，B4 GALT 1的过表达恢复了生长，并赋予了对ZFX沉默细胞的耐药性。总之，我们已经证明，ZFX是异常表达在多种人类白血病细胞，它调节白血病细胞的生长和药物反应部分通过B4 GALT 1，这表明，ZFX是一种新的调节剂白血病细胞，并值得深入研究这种“干性”调节剂在这些致命的疾病。
Zinc finger protein X-linked (ZFX) is a key regulator of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), which is required for both Notch intracellular domain (NotchIC)-induced acute T-cell leukemia and MLL-AF9-induced myeloid leukemia in mouse models. However, the role of ZFX and its underlying mechanism in human leukemic cells remain unclear yet, though accumulating data have demonstrated that ZFX is aberrantly expressed in various human tumors and plays an important role. Herein, we found thatZFXwas aberrantly expressed in various human leukemic cell lines and primary cells from leukemia patients compared with control cells. The silence of ZFX led to the growth suppression through either the deregulated cell cycle or the induction of apoptosis in various cells including K562, Jurkat, Namalwa, and THP-1 cells. The gene expression analysis revealed that UDP-Gal:βGlcNAc β 1,4-galactosyltransferase, polypeptide 1 (B4GALT1) was significantly down-regulated upon ZFX silencing, which is implicated in the response of K562 cells to the treatment of imatinib mesylate (IM). In addition, lectin blot assay showed that the galactosylation of glycoproteins in K562 cells was suppressed upon ZFX silencing. Interestingly, overexpression of B4GALT1 restored the growth and conferred drug resistance to ZFX-silenced cells. Taken together, we have demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this ‘stemness’ regulator in these deadly diseases.