Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Biomed Pharmacother. 2017 Nov;95:1504-1513. doi: 10.1016/j.biopha.2017.08.097. Epub 2017 Sep 21.
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.
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.
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.
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.
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。
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。
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。
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。