ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway
ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway
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ETV6 通过介导 Raf/MEK/ERK 通路调节氯化血红素诱导的 K562 细胞红系分化
DOI：
10.1248/bpb.b21-00632
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发表时间：
2022-03-01
影响因子：
2
通讯作者：
Liu, Shuqing
中科院分区：
文献类型：
--
作者：
Li, Zhaopeng;Sun, Ming-Zhong;Liu, Shuqing
作为转录因子E-26（ETS）家族的成员，ETS变体6（ETV6）在造血和胚胎发育中发挥着重要作用。 ETV6表达异常还参与癌症和白血病的发生、发展和进展。在目前的工作中，我们假设 ETV6 在慢性粒细胞白血病 (CML) 的红细胞分化中发挥作用。我们发现ETV6的蛋白表达水平在氯化血红素诱导的K562细胞红系分化过程中显着上调。此外，ETV6的过表达抑制了血红素诱导的K562细胞中的红系分化，联苯胺阳性细胞数量减少，红系分化特异性标记物糖蛋白（GPA）、CD71、血红蛋白A（HBA）、α-珠蛋白、γ-珠蛋白和ε-珠蛋白的表达水平降低。相反，ETV6 敲除促进了氯化血红素诱导的 K562 细胞的红系分化。此外，ETV6表达水平与用氯化血红素处理的K562细胞的增殖能力略有正相关。从机制上讲，ETV6过表达抑制纤维肉瘤/丝裂原激活的细胞外信号调节激酶/细胞外调节蛋白激酶（Raf/MEK/ERK）通路，ETV6敲低激活Raf/MEK/ERK通路。总的来说，目前的工作表明ETV6通过Raf/MEK/ERK通路在调节K562细胞红系分化中发挥抑制作用，它将成为红细胞生成障碍的潜在治疗靶点。
As a member of transcription factor E-Twenty Six (ETS) family, ETS variant 6 (ETV6) plays significant role in hematopoiesis and embryonic development. ETV6 dysexpression also involved in the occurrence, de-velopment and progression of cancers and leukemia. In current work, we hypothesized that ETV6 plays a role in erythroid differentiation of chronic myeloid leukemia (CML). We found the protein expression level of ETV6 was significantly upregulated during hemin-induced erythroid differentiation of K562 cells. More-over, overexpression of ETV6 inhibited erythroid differentiation in hemin-induced K562 cells with decreased numbers of benzidine-positive cells and decreased expression levels of erythroid differentiation specific markers glycophorin (GPA), CD71, hemoglobin A (HBA), alpha-globin, gamma-globin and epsilon-globin. Conversely, ETV6 knockdown promoted erythroid differentiation in hemin-induced K562 cells. Furthermore, ETV6 expression level slightly positively with the proliferation capacity of K562 cells treated with hemin. Mechanistically, ETV6 overexpression inhibited fibrosarcoma/mitogen activated extracellular signal-regulated kinase/extra-cellular regulated protein kinase (Raf/MEK/ERK) pathway, ETV6 knockdown activated the Raf/MEK/ERK pathway. Collectively, the current work demonstrates that ETV6 plays an inhibitory role in the regulation of K562 cell erythroid differentiation via Raf/MEK/ERK pathway, it would be a potentially therapeutic target for dyserythropoiesis.