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长链非编码 RNA ZEB1-AS1 通过调控 miR-577 促进胶质瘤细胞的增殖、迁移和侵袭。

Long non-coding RNA ZEB1-AS1 promotes glioma cell proliferation, migration and invasion through regulating miR-577.

机构信息

Department of Clinical Laboratory, Linyi Chest Hospital, Linyi, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 May;22(10):3085-3093. doi: 10.26355/eurrev_201805_15068.

Abstract

OBJECTIVE

Long non-coding RNA ZEB1-AS1 (ZEB1-AS1) was reported to be implicated and aberrantly expressed in multiple cancers. However, the potential mechanism and clinical significance of ZEB1-AS1 in the carcinogenesis of glioma remain unclear.

PATIENTS AND METHODS

RT-PCR was performed to determine the expression of ZEB1-AS1 in glioma tissues and cell lines. The association between ZEB1-AS1 expression and clinical features and prognosis were statistically analyzed. MTT and transwell assays were used to test the proliferation, invasion, and migration of glioma cells. Luciferase report assay was used to detect the correlation between ZEB1-AS1 and miR-577 in glioma.

RESULTS

Compared with normal brain tissues and cells, ZEB1-AS1 in glioma tissues and cell lines was shown to be expressed at high levels. Clinical association analysis indicated that ZEB1-AS1 expression was closely associated with tumor size (p = 0.014), KPS (p = 0.004) and WHO grade (p = 0.001). In addition, it was observed that high expression level of ZEB1-AS1 was remarkably associated with overall survival and could be an independent prognostic indicator of glioma using univariate and multivariate analysis. Functional experiments demonstrated that down-regulation of ZEB1-AS1 suppressed the proliferation, invasion, and migration of glioma cell in vitro. In the mechanism, we found that ZEB1-AS1 acted as a competing endogenous RNA to sponge miR-577. Moreover, miR-577 could reverse the tumor-promotive role of ZEB1-AS1 on glioma cells.

CONCLUSIONS

Our findings demonstrated that ZEB1-AS1 might play an oncogenic role in glioma and was a poor prognostic factor. The ZEB1-AS1/miR-577 axis might be a potential target for the development of effective glioma therapy.

摘要

目的

长链非编码 RNA ZEB1-AS1(ZEB1-AS1)已被报道在多种癌症中存在并异常表达。然而,ZEB1-AS1 在胶质瘤发生中的潜在机制和临床意义尚不清楚。

患者和方法

采用 RT-PCR 检测胶质瘤组织和细胞系中 ZEB1-AS1 的表达。统计分析 ZEB1-AS1 表达与临床特征和预后的关系。MTT 和 Transwell 实验检测胶质瘤细胞的增殖、侵袭和迁移。荧光素酶报告实验检测 ZEB1-AS1 与 miR-577 在胶质瘤中的相关性。

结果

与正常脑组织和细胞相比,胶质瘤组织和细胞系中 ZEB1-AS1 的表达水平较高。临床相关性分析表明,ZEB1-AS1 的表达与肿瘤大小(p = 0.014)、KPS(p = 0.004)和 WHO 分级(p = 0.001)密切相关。此外,高表达 ZEB1-AS1 与总生存期显著相关,且通过单因素和多因素分析,ZEB1-AS1 可作为胶质瘤的独立预后指标。功能实验表明,下调 ZEB1-AS1 可抑制胶质瘤细胞的体外增殖、侵袭和迁移。在机制上,我们发现 ZEB1-AS1 作为竞争性内源性 RNA 可吸附 miR-577。此外,miR-577 可逆转 ZEB1-AS1 对胶质瘤细胞的促肿瘤作用。

结论

本研究表明,ZEB1-AS1 可能在胶质瘤中发挥致癌作用,是一个不良的预后因素。ZEB1-AS1/miR-577 轴可能是开发有效胶质瘤治疗方法的潜在靶点。

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