Pourkeramati Fatemeh, Asadi Malek Hossein, Shakeri Shahryar, Farsinejad Alireza
Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Iran Biomed J. 2019 Jan;23(1):47-56. doi: 10.29252/.23.1.47. Epub 2018 May 13.
ZFX is a transcriptional regulator in embryonic stem cells and plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood.
We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR.
The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors, demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants.
Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.
ZFX是胚胎干细胞中的一种转录调节因子,在多能性和自我更新中发挥重要作用。ZFX在多能干细胞中广泛表达,在胚胎干细胞分化过程中表达下调。ZFX有五种不同的变体,编码三种不同的蛋白质异构体。虽然有几份报告确定了ZFX在多种体细胞癌中的过表达,但ZFX剪接变体在癌细胞中的表达尚不清楚。
我们使用定量PCR研究了一系列乳腺癌组织和细胞系中ZFX变体的表达。
与边缘组织相比,肿瘤组织中ZFX变体1/3的表达更高。相反,ZFX变体5在肿瘤组织中表达下调。虽然ZFX变体1/3和ZFX变体5的表达在低级别肿瘤中显著增加,但ZFX变体4在高级别肿瘤中强烈表达,表明有淋巴浸润。此外,我们的结果揭示了HER2状态与ZFX剪接变体表达之间的显著关联。
我们的数据表明,ZFX剪接转录本的表达在不同类型的乳腺癌之间存在差异,可能有助于其肿瘤发生过程。因此,ZFX剪接转录本可被视为新型肿瘤标志物,在乳腺癌的诊断、预后和治疗中可能具有价值。