ZRANB2/SNHG20/FOXK1 轴调控胶质瘤中脉管生成拟态的形成。

ZRANB2/SNHG20/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma.

机构信息

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, 110004, China.

出版信息

J Exp Clin Cancer Res. 2019 Feb 11;38(1):68. doi: 10.1186/s13046-019-1073-7.

BACKGROUND

Glioma is the most common intracranial neoplasm with vasculogenic mimicry formation as one form of blood supply. Many RNA-binding proteins and long non-coding RNAs are involved in tumorigenesis of glioma.

METHODS

The expression of ZRANB2, SNHG20 and FOXK1 in glioma were detected by real-time PCR or western blot. The function of ZRANB2/SNHG20/FOXK1 axis in glioma associated with vasculogenic mimicry formation was analyzed.

RESULTS

ZRANB2 is up-regulated in glioma tissues and glioma cells. ZRANB2 knockdown inhibits the proliferation, migration, invasion and vasculogenic mimicry formation of glioma cells. ZRANB2 binds to SNHG20 and increases its stability. Knockdown of SNHG20 reduces the degradation of FOXK1 mRNA by SMD pathway. FOXK1 inhibits transcription by binding to the promoters of MMP1, MMP9 and VE-Cadherin and inhibits vasculogenic mimicry formation of glioma cells.

CONCLUSIONS

ZRANB2/SNHG20/FOXK1 axis plays an important role in regulating vasculogenic mimicry formation of glioma, which might provide new targets of glioma therapy.

背景

神经锌指蛋白 2（ZRANB2）是一种锌指 RNA 结合蛋白，在多种肿瘤中异常表达并发挥癌基因作用。长链非编码 RNA（lncRNA）SNHG20 异常高表达与多种肿瘤的发生发展密切相关。叉头框转录因子 K1（FOXK1）是 FOX 转录因子家族的成员之一，与肿瘤的发生发展有关。本研究旨在探讨 ZRANB2 对胶质瘤细胞血管形成拟态形成的作用及机制。

方法

实时荧光定量 PCR 或 Western blot 检测胶质瘤组织和细胞中 ZRANB2、SNHG20 和 FOXK1 的表达。分析 ZRANB2/SNHG20/FOXK1 轴在胶质瘤相关血管形成拟态形成中的作用。

结果

ZRANB2 在胶质瘤组织和细胞中表达上调。ZRANB2 knockdown 抑制胶质瘤细胞的增殖、迁移、侵袭和血管形成拟态形成。ZRANB2 与 SNHG20 结合并增加其稳定性。SNHG20 的敲低通过 SMD 途径减少 FOXK1 mRNA 的降解。FOXK1 通过结合 MMP1、MMP9 和 VE-Cadherin 的启动子抑制转录，从而抑制胶质瘤细胞的血管形成拟态形成。