Zfp521 promotes B-cell viability and cyclin D1 gene expression in a B cell culture system.
Zfp521 promotes B-cell viability and cyclin D1 gene expression in a B cell culture system.
复制标题
ZFP521在B细胞培养系统中促进B细胞活力和细胞周期蛋白D1基因表达。
DOI：
10.1016/j.leukres.2016.03.013
复制
发表时间：
2016-07
影响因子：
2.7
通讯作者：
Hentges KE
中科院分区：
文献类型：
--
作者：
Al Dallal S;Wolton K;Hentges KE
在BCL1细胞培养中，敲低Zfp521可降低细胞活力，促进细胞凋亡。在Zfp521敲低的细胞中，B细胞中表达的基因下调。Zfp521过表达的小鼠肿瘤中Cyclin D1表达增加。白血病是由造血祖细胞增殖失调引起的。多步骤承诺过程中的错误导致未成熟淋巴细胞数量过多，导致恶性疾病。参与淋巴细胞分化的基因常与白血病有关。其中一个基因，Zfp521，被发现当过度表达时会导致小鼠b细胞白血病。Zfp521在b细胞分化中的作用及其导致白血病转化的机制尚不清楚。在这项研究中，我们报道了Zfp521敲低导致b细胞培养系统的凋亡，并促进在b细胞分化后期作用的基因的下调。我们确定了Pax5和cyclin D1是Zfp521的靶基因，并提出在Zfp521基因附近插入逆转录病毒的小鼠中观察到的过度b细胞增殖是由于b细胞中cyclin D1的上调。总的来说，这些结果表明Zfp521失调与b细胞存活之间存在联系。
Knockdown of Zfp521 in BCL1 cell culture reduces viability and promotes apoptosis. Genes expressed in B cells are down-regulated in cells with Zfp521 knockdown. Cyclin D1 expression is increased in mouse tumors with Zfp521 over-expression. Leukemia arises due to the dysregulated proliferation of hematopoietic progenitor cells. Errors in the multi-step commitment process result in excessive numbers of immature lymphocytes, causing malignant disease. Genes involved in the differentiation of lymphocytes are often associated with leukemia. One such gene, Zfp521, has been found to cause B-cell leukemia in mice when over-expressed. The role of Zfp521 in B-cell differentiation, and the mechanisms by which it leads to leukemic transformation, are unclear. In this study we report that Zfp521 knockdown causes apoptosis in a B-cell culture system and promotes down-regulation of genes acting at late stages of B-cell differentiation. We identify Pax5 and cyclin D1 as Zfp521 target genes, and suggest that excessive B-cell proliferation observed in mice with retroviral insertions near the Zfp521 gene is due to an up-regulation of cyclin D1 in B-cells. Overall, these results suggest links between dysregulated Zfp521 and B-cell survival.