ZNF268在卵巢癌细胞中的异常表达可导致细胞生长和迁移行为发生改变.doc

  Aberrant Expression of ZNF268 Alters the Growth and Migration of Ovarian Cancer Cells# 5 10 15 20 25 30 35 40  Abstract: Ovarian cancer is one of the most lethal gynaecologic cancers worldwide. However, the mechanism underlying ovarian carcinogenesis is not well understood. Here, we show that ZNF268 is overexpressed in human ovarian carcinomas. ZNF268 knockdown increased the viability, colony formation, and the growth of in vivo xenografts of ovarian carcinoma SKOV-3 cells, whereas SKOV-3 cell migration was inhibited by ZNF268 knockdown. Furthermore, we demonstrated that ZNF268 knockdown may increase SKOV-3 cell growth by promoting cell cycle progression. Our findings suggest that ZNF268 is a novel protein involved in ovarian carcinogenesis and may help us better understand the mechanism of ovarian carcinogenesis. Key words: ZNF268; Ovarian cancer; SKOV-3 cells 0 Introduction Krüppel-associated box (KRAB)-containing zinc finger (KRAB-ZNF) proteins, which represent the largest single family of transcriptional regulators in mammals [1], have been shown to regulate gene expression by binding to target DNA sequences through the zinc finger domain, thereby allowing KRAB to repress transcription [2,3]. Nevertheless, little is known about the biological functions of KRAB-ZNF proteins [4]. ZNF268, which was isolated from a human embryo cDNA library [5], is a typical KRAB-containing zinc finger protein that has been found to produce eight splice variants and be translated into two proteins: ZNF268a and ZNF268b2 [6]. ZNF268a contains a KRAB domain and as many as 24 zinc fingers and may function as a transcriptional repressor [7], while ZNF268b2 consists of only the zinc finger domain and contributes to human cervical cancer via NF-κB signalling pathway [8]. The ZNF268 promoter is located in the first exon of the gene and can be regulated by cAMP response element binding protein 2 (CREB-2) [9]. Previous studies suggest that ZNF268 may be involved in human foetal liver de