Previously, we reported that ZNF300 might play a role in leukemogenesis. In this study, we further investigated the function of ZNF300 in K562 cells undergoing differentiation. We found that ZNF300 upregulation in K562 cells coincided with megakaryocytic differentiation induced by phorbol-12-myristate-13-acetate (PMA) or erythrocytic differentiation induced by cytosine arabinoside (Ara-C), respectively. To further test whether ZNF300 upregulation promoted differentiation, we knocked down ZNF300 and found that ZNF300 knockdown effectively abolished PMA-induced megakaryocytic differentiation, evidenced by decreased CD61 expression. Furthermore, Ara-C-induced erythrocytic differentiation was also suppressed in ZNF300 knockdown cells with decreased γ-globin expression and CD235a expression. These observations suggest that ZNF300 may be a critical factor controlling distinct aspects of K562 cells. Indeed, ZNF300 knockdown led to increased cell proliferation. Consistently, ZNF300 knockdown cells exhibited an increased percentage of cells at S phase accompanied by decreased percentage of cells at G0/G1 and G2/M phase. Increased cell proliferation was further supported by the increased expression of cell proliferation marker PCNA and the decreased expression of cell cycle regulator p15 and p27. In addition, MAPK/ERK signaling was significantly suppressed by ZNF300 knockdown. These findings suggest a potential mechanism by which ZNF300 knockdown may impair megakaryocytic and erythrocytic differentiation.

中文翻译：

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ZNF300组合物可抑制佛波醇引起的强迫性巨核细胞分化，以及阿拉伯呋喃糖基胞苷对K562细胞的红细胞分化的抑制作用。

先前，我们报道ZNF300可能在白血病发生中起作用。在这项研究中，我们进一步研究了ZNF300在经历分化的K562细胞中的功能。我们发现，K562细胞中ZNF300的上调与分别由佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的巨核细胞分化或胞嘧啶阿拉伯糖苷（Ara-C）诱导的红细胞分化相吻合。为了进一步测试ZNF300的上调是否促进分化，我们敲低了ZNF300，发现ZNF300的敲低有效地消除了PMA诱导的巨核细胞分化，这由CD61表达降低所证明。此外，在ZNF300敲低的细胞中，Ara-C诱导的红细胞分化也受到抑制，γ-珠蛋白表达和CD235a表达降低。这些观察结果表明ZNF300可能是控制K562细胞不同方面的关键因素。确实，ZNF300敲低导致细胞增殖增加。一致地，ZNF300敲低的细胞在S期的细胞百分比升高，而在G0 / G1和G2 / M期的细胞百分比降低。细胞增殖标记物PCNA的表达增加和细胞周期调节因子p15和p27的表达减少，进一步支持了细胞增殖的增加。此外，ZAPK300的敲低显着抑制了MAPK / ERK信号传导。这些发现提示ZNF300敲低可能损害巨核细胞和红细胞分化的潜在机制。ZNF300敲低的细胞在S期的细胞百分比升高，而在G0 / G1和G2 / M期的细胞百分比降低。细胞增殖标记物PCNA的表达增加和细胞周期调节因子p15和p27的表达减少，进一步支持了细胞增殖的增加。此外，ZAPK300的敲低显着抑制了MAPK / ERK信号传导。这些发现提示ZNF300敲低可能损害巨核细胞和红细胞分化的潜在机制。ZNF300敲低的细胞在S期的细胞百分比升高，而在G0 / G1和G2 / M期的细胞百分比降低。细胞增殖标记物PCNA的表达增加和细胞周期调节因子p15和p27的表达减少，进一步支持了细胞增殖的增加。此外，ZAPK300的敲低显着抑制了MAPK / ERK信号传导。这些发现提示ZNF300敲低可能损害巨核细胞和红细胞分化的潜在机制。此外，ZAPK300的敲低显着抑制了MAPK / ERK信号传导。这些发现提示ZNF300敲低可能损害巨核细胞和红细胞分化的潜在机制。此外，ZAPK300的敲低显着抑制了MAPK / ERK信号传导。这些发现提示ZNF300敲低可能损害巨核细胞和红细胞分化的潜在机制。