ZNF300 knockdown inhibits forced megakaryocytic differentiation by phorbol and erythrocytic differentiation by arabinofuranosyl cytidine in K562 cells.
ZNF300 knockdown inhibits forced megakaryocytic differentiation by phorbol and erythrocytic differentiation by arabinofuranosyl cytidine in K562 cells.
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ZNF300 敲低可抑制 K562 细胞中佛波醇强制巨核细胞分化和阿拉伯呋喃糖胞苷强制红细胞分化。
DOI：
10.1371/journal.pone.0114768
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Cai J;Gong R;Yan F;Yu C;Liu L;Wang W;Lin Y;Guo M;Li W;Huang Z
此前，我们曾报道ZNF300可能在白血病的发生中起作用。在本研究中，我们进一步研究了ZNF300在K562细胞分化过程中的作用。我们发现，ZNF300在K562细胞中的上调分别与佛波酯(PMA)诱导的巨核细胞分化和阿糖胞苷(Ara-C)诱导的红细胞分化相一致。为了进一步测试ZNF300上调是否促进分化，我们下调了ZNF300，发现ZNF300基因敲除后有效地取消了PMA诱导的巨核细胞分化，CD61的表达下降就是明证。此外，在ZNF300基因敲除细胞中，Ara-C诱导的红细胞分化也被抑制，γ-珠蛋白和CD235a的表达降低。这些观察表明，ZNF300可能是控制K562细胞不同方面的关键因素。事实上，ZNF300基因敲除导致了细胞增殖的增加。ZNF300基因敲除细胞始终表现为S期细胞比例增加，而G0/G1期和G2/M期细胞比例下降。细胞增殖标记物PCNA的表达增加，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，ZNF300基因敲除可显著抑制MAPK/ERK信号转导。这些发现提示了ZNF300基因敲除可能损害巨核细胞和红细胞分化的潜在机制。
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.
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影响因子：
12.3
作者：
Urrutia R
通讯作者：
Urrutia R
影响因子：
5.3
作者：
Wang T;Wang XG;Xu JH;Wu XP;Qiu HL;Yi H;Li WX
通讯作者：
Li WX
影响因子：
2.7
作者：
LOZZIO, BB;LOZZIO, CB
通讯作者：
LOZZIO, CB
影响因子：
2.1
作者：
Takagaki, K;Katsuma, S;Yano, J
通讯作者：
Yano, J
KAP1结合的全基因组分析表明KRAB-ZNF的自动调节。
影响因子：
4.5
作者：
O'Geen, Henriette;Squazzo, Sharon L.;Iyengar, Sushma;Blahnik, Kim;Rinn, John L.;Chang, Howard Y.;Green, Roland;Farnham, Peggy J.
通讯作者：
Farnham, Peggy J.