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HOXA11-AS/miR-214-3p/EZH2 轴对胶质瘤细胞生长、迁移和侵袭的调节作用。

Regulation of HOXA11-AS/miR-214-3p/EZH2 axis on the growth, migration and invasion of glioma cells.

机构信息

Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.

Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.

出版信息

Biomed Pharmacother. 2017 Nov;95:1504-1513. doi: 10.1016/j.biopha.2017.08.097. Epub 2017 Sep 21.

Abstract

BACKGROUND

Glioma is one of the most common and aggressive malignant tumors in central nervous system. Recently, long non-coding RNA (lncRNA) HOXA11-AS has been reported to be an oncogenic gene in multiple cancers. However, the molecular mechanisms of HOXA11-AS involved in cancer progression of human glioma remain unknown.

MATERIALS AND METHODS

The expression levels of HOXA11-AS in 45 paired primary glioma tissues and cell lines were examined by quantitative real-time PCR, and the correlation between HOXA11-AS expression and clinicopathologic characteristics of patients with glioma were analyzed. HOXA11-AS was knockdown in glioma cells by transfection with HOXA11-AS siRNA, and cell proliferation, migration and invasion were detected. The tumor growth of xenografts with HOXA11-AS knockdown glioma cells was also analyzed.

RESULTS

The expression levels of HOXA11-AS were significantly up-regulated in glioma tissues and cell lines compared with that in adjacent normal brain tissues and normal human astrocytes (NHA). High expression of HOXA11-AS was correlated with shorter overall survival in patients with glioma. Knockdown of HOXA11-AS inhibited glioma cell proliferation, migration and invasion in vitro, and tumor growth in vivo. In addition, we demonstrated that HOXA11-AS functioned as a competing endogenous RNA (ceRNA) for miR-214-3p, which in turn positively regulated the expression of its direct target EZH2.

CONCLUSIONS

We demonstrated that HOXA11-AS acted as an oncogenic lncRNA that promoted cell growth and metastasis of glioma through regulating miR-214-3p/EZH2 axis. These results suggested HOXA11-AS may serve as an efficient marker and a potential therapeutic target for glioma.

摘要

背景

神经胶质瘤是中枢神经系统最常见和最具侵袭性的恶性肿瘤之一。最近,长链非编码 RNA(lncRNA)HOXA11-AS 已被报道在多种癌症中是致癌基因。然而,HOXA11-AS 参与人脑胶质瘤发生发展的分子机制尚不清楚。

材料与方法

通过实时定量 PCR 检测 45 对原发性脑胶质瘤组织和细胞系中 HOXA11-AS 的表达水平,并分析 HOXA11-AS 表达与脑胶质瘤患者临床病理特征的相关性。通过转染 HOXA11-AS siRNA 敲低脑胶质瘤细胞中的 HOXA11-AS,检测细胞增殖、迁移和侵袭。还分析了敲低 HOXA11-AS 的脑胶质瘤细胞的异种移植瘤的生长情况。

结果

与邻近正常脑组织和正常人星形胶质细胞(NHA)相比,HOXA11-AS 在脑胶质瘤组织和细胞系中的表达水平显著上调。HOXA11-AS 高表达与脑胶质瘤患者总生存期缩短相关。HOXA11-AS 敲低抑制了体外脑胶质瘤细胞的增殖、迁移和侵袭,并抑制了体内肿瘤的生长。此外,我们证明 HOXA11-AS 作为 miR-214-3p 的竞争性内源 RNA(ceRNA)发挥作用,miR-214-3p 又正向调节其直接靶基因 EZH2 的表达。

结论

我们证明 HOXA11-AS 作为一种致癌 lncRNA,通过调节 miR-214-3p/EZH2 轴促进脑胶质瘤细胞的生长和转移。这些结果表明 HOXA11-AS 可能作为脑胶质瘤的有效标志物和潜在治疗靶点。

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