Inhibition of DLX-7 homeobox gene causes decreased expression of GATA-1 and c-myc genes and apoptosis.
Inhibition of DLX-7 homeobox gene causes decreased expression of GATA-1 and c-myc genes and apoptosis.
复制标题
抑制 DLX-7 同源盒基因会导致 GATA-1 和 c-myc 基因表达降低以及细胞凋亡。
DOI：
10.1073/pnas.94.7.3245
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发表时间：
1997
影响因子：
11.1
通讯作者：
Takeshita,K
中科院分区：
文献类型：
--
作者：
Shimamoto,T;Nakamura,S;Bollekens,J;Ruddle,FH;Takeshita,K
DLX基因家族是与果蝇远端(Drosophiladistal-less)(Dll)基因相关的不同同源框基因家族，并且据报道主要在前脑和颅面结构中表达。我们之前已经确定了这个家族的一个新成员，DLX-7。我们现在报道该基因在正常造血细胞和具有红系特征的白血病细胞系中表达。我们使用针对DLX-7mRNA翻译起始位点的反义寡核苷酸来抑制其在高水平表达DLX-7的人红白血病细胞系K562中的表达。反义寡核苷酸有效地减少DLX-7mRNA，而对照寡核苷酸，包括除了四个核苷酸错配之外与反义序列相同的突变寡核苷酸，对DLX-7mRNA水平没有影响。与对照相比，DLX-7表达的抑制使铺板效率降低约70%。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-地高辛缺口末端标记（TUNEL）方法显示，反义处理引起细胞凋亡。反义治疗下调DLX-7表达与GATA-1和c-mycmRNA水平降低相关。因此，我们得出结论，DLX-7在造血细胞中表达，并且其表达的抑制导致GATA-1和c-myc基因水平降低，并伴随诱导细胞凋亡。
TheDLXgene family is a family of divergent homeobox genes which are related to theDrosophiladistal-less (Dll) gene and has been reported to be expressed primarily in the forebrain and craniofacial structures. We have previously identified a new member of this family,DLX-7. We now report that this gene is expressed in normal hematopoietic cells and leukemia cell lines with erythroid characteristics. We used an antisense oligonucleotide targeted against the translation start site ofDLX-7mRNA to inhibit its expression in a human erythroleukemia cell line K562, which expressesDLX-7at a high level. The antisense oligonucleotide efficiently reduced theDLX-7mRNA, while control oligonucleotides, including a mutant oligonucleotide identical to the antisense sequence except for four nucleotide mismatches, had no effect onDLX-7mRNA level. Inhibition ofDLX-7expression decreased the plating efficiency by ≈70% compared with control. The antisense treatment caused apoptosis, as shown by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) method. Down-regulation ofDLX-7expression by antisense treatment was associated with a reduction inGATA-1and c-mycmRNA levels. Thus, we conclude thatDLX-7is expressed in hematopoietic cells and that the inhibition of its expression results in the decreased levels ofGATA-1and c-mycgenes, with an accompanying induction of apoptosis.