沉默 ZEB2 诱导脑胶质瘤细胞系凋亡并降低其活力。

Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.

Hematology Division, Immunology Department, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.

出版信息

Molecules. 2021 Feb 9;26(4):901. doi: 10.3390/molecules26040901.

DOI:10.3390/molecules26040901

PMID:33572092

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7916008/

Abstract

BACKGROUND

Glioma is an aggressive type of brain tumor that originated from neuroglia cells, accounts for about 80% of all malignant brain tumors. Glioma aggressiveness has been associated with extreme cell proliferation, invasion of malignant cells, and resistance to chemotherapies. Due to resistance to common therapies, glioma affected patients' survival has not been remarkably improved. ZEB2 (SIP1) is a critical transcriptional regulator with various functions during embryonic development and wound healing that has abnormal expression in different malignancies, including brain tumors. ZEB2 overexpression in brain tumors is attributed to an unfavorable state of the malignancy. Therefore, we aimed to investigate some functions of ZEB2 in two different glioblastoma U87 and U373 cell lines.

METHODS

In this study, we investigated the effect of ZEB2 knocking down on the apoptosis, cell cycle, cytotoxicity, scratch test of the two malignant brain tumor cell lines U87 and U373. Besides, we investigated possible proteins and microRNA, SMAD2, SMAD5, and miR-214, which interact with ZEB2 via in situ analysis. Then we evaluated candidate gene expression after ZEB2-specific knocking down.

RESULTS

We found that ZEB2 suppression induced apoptosis in U87 and U373 cell lines. Besides, it had cytotoxic effects on both cell lines and reduced cell migration. Cell cycle analysis showed cell cycle arrest in G0/G1 and apoptosis induction in U87 and U373 cell lines receptively. Also, we have found that SAMAD2/5 expression was reduced after ZEB2-siRNA transfection and miR-214 upregulated after transfection.

CONCLUSIONS

In line with previous investigations, our results indicated a critical oncogenic role for ZEB2 overexpression in brain glioma tumors. These properties make ZEB2 an essential molecule for further studies in the treatment of glioma cancer.

摘要

背景

神经胶质瘤是一种源自神经胶质细胞的侵袭性脑肿瘤，约占所有恶性脑肿瘤的 80%。神经胶质瘤的侵袭性与细胞极度增殖、恶性细胞浸润以及对化疗的耐药性有关。由于对常规治疗的耐药性，神经胶质瘤患者的生存状况并未得到显著改善。ZEB2（SIP1）是一种关键的转录调节因子，在胚胎发育和伤口愈合过程中有多种功能，在包括脑肿瘤在内的不同恶性肿瘤中异常表达。脑肿瘤中 ZEB2 的过表达归因于恶性肿瘤的不利状态。因此，我们旨在研究 ZEB2 在两种不同的脑胶质瘤 U87 和 U373 细胞系中的一些功能。

方法

在这项研究中，我们研究了 ZEB2 敲低对两种恶性脑肿瘤细胞系 U87 和 U373 的细胞凋亡、细胞周期、细胞毒性、划痕试验的影响。此外，我们通过原位分析研究了与 ZEB2 相互作用的可能蛋白质和 microRNA（SMAD2、SMAD5 和 miR-214）。然后，我们评估了 ZEB2 特异性敲低后候选基因的表达。

结果

我们发现 ZEB2 抑制诱导了 U87 和 U373 细胞系的细胞凋亡。此外，它对两种细胞系均具有细胞毒性作用，并减少了细胞迁移。细胞周期分析显示，U87 和 U373 细胞系分别发生细胞周期阻滞在 G0/G1 期和凋亡诱导。此外，我们发现 ZEB2-siRNA 转染后 SAMAD2/5 表达减少，miR-214 转染后上调。