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微小RNA-224靶向ERG2并促进脑膜瘤的恶性进展。

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma.

作者信息

Wang Maomao, Deng Xiaodong, Ying Qi, Jin Tingyan, Li Ming, Liang Chong

机构信息

The 411 Hospital of PLA, Department of Neurosurgery, 15 Dongjiangwan Road, Shanghai 200081, China.

The 81 Hospital of PLA, Department of Neurosurgery, 34 Taiping Road, Nanjing 210002, China.

出版信息

Biochem Biophys Res Commun. 2015 May 1;460(2):354-61. doi: 10.1016/j.bbrc.2015.03.038. Epub 2015 Mar 14.

Abstract

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan-Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan-Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas.

摘要

微小RNA-224在多种预后不良的恶性肿瘤中过表达,其在包括细胞增殖、凋亡以及多个发育和生理进程等生物学过程中发挥关键作用。然而,miR-224与脑膜瘤患者临床结局之间的潜在关联仍不清楚。在此,我们研究了miR-224在脑膜瘤中的表达及生物学功能。通过Northern印迹分析和定量逆转录-聚合酶链反应(qRT-PCR)检测脑膜瘤组织和正常脑组织中miR-224的表达。采用Kaplan-Meier分析和Cox回归分析来检验其与临床病理特征的相关性及预后价值。通过MTT法和凋亡检测法检测miR-224对脑膜瘤细胞增殖和凋亡的生物学作用。我们发现,miR-224在脑膜瘤组织中的表达水平显著高于正常脑组织,且与高级别病理分级呈正相关。Kaplan-Meier分析表明,miR-224表达低的脑膜瘤患者总体生存期和无复发生存期显著延长。此外,我们在体外证实ERG2是miR-224的一个共同候选靶基因。我们的结果表明,miR-224的下调抑制细胞生长,并通过激活ERG2-BAK诱导的凋亡途径增强细胞凋亡。我们的研究结果提示,miR-224表达可预测脑膜瘤患者的总体生存期和无复发生存期,它可能是治疗恶性脑膜瘤的一个有前景的治疗靶点。

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