Karami Madani GholamReza, Rad Abolfazl, Molavi Mehdi, Ardalan Khales Sima, Abbaszadegan Mohammad Reza, Forghanifard Mohammad Mahdi
Department of Biology, Damghan Branch, Islamic Azad University, Cheshmeh-Ali Boulevard, Sa'dei Square, P.O. Box: 3671639998, Damghan, Iran.
Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
J Gastrointest Cancer. 2018 Dec;49(4):437-441. doi: 10.1007/s12029-017-9985-y.
Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. Deregulation of EZH2 in cancers is correlated with tumor cell invasiveness, metastasis, and the patients' poor outcome. However, the mechanistic role of EZH2 in cancer is ambiguous. In this study, we aimed to inhibit the expression of EZH2 in a cancer cell line, and evaluate consequence changes in gene expression pattern.
Using specific retroviral shRNA-EZH2, EZH2 gene was silenced in the KYSE30 cell line. Relative comparative real-time PCR was used to confirm silencing of EZH2 and evaluate expression pattern of selected markers.
Inhibition of EZH2 expression in KYSE30 cells caused significant changes in different genes. Indeed, HIWI and HEY1 genes were over- and underexpressed in KYSE30 cells, respectively, following EZH2 silencing. Other selected cancer stem cell markers were not changed significantly.
To the best our knowledge, there are variety of small molecule inhibitors to target EZH2 in cancer cells as a treatment candidate; therefore, our data in this study helps the researchers to select EZH2 for cancer therapy based on its mechanism and correlation with other markers.
zeste 同源物 2 增强子(EZH2)是一种干性因子,在细胞分化、胚胎发育以及癌症进展的调控中发挥作用。癌症中 EZH2 的失调与肿瘤细胞的侵袭性、转移以及患者的不良预后相关。然而,EZH2 在癌症中的作用机制尚不明确。在本研究中,我们旨在抑制癌细胞系中 EZH2 的表达,并评估基因表达模式的相应变化。
使用特异性逆转录病毒 shRNA-EZH2 在 KYSE30 细胞系中沉默 EZH2 基因。采用相对比较实时定量 PCR 来确认 EZH2 的沉默并评估所选标志物的表达模式。
KYSE30 细胞中 EZH2 表达的抑制导致不同基因发生显著变化。实际上,EZH2 沉默后,KYSE30 细胞中 HIWI 和 HEY1 基因分别出现过表达和低表达。其他所选的癌症干细胞标志物未发生显著变化。
据我们所知,有多种小分子抑制剂可作为治疗候选物靶向癌细胞中的 EZH2;因此,我们在本研究中的数据有助于研究人员根据其机制以及与其他标志物的相关性来选择 EZH2 用于癌症治疗。