Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650050, P.R. China.
Oncol Rep. 2017 Nov;38(5):3177-3186. doi: 10.3892/or.2017.5986. Epub 2017 Sep 21.
Emerging evidence suggests that long non-coding RNAs (lncRNAs) may be involved in modulating various aspects of tumor biology and serve as potential therapeutic targets as well as novel biomarkers in the treatment of glioma. The present study investigated the role of lncRNA, Prader Willi/Angelman region RNA 5 (PAR5; also known as PWAR5), in glioma and its clinical significance in glioma cases. The expression levels of PAR5 were determined in clinical samples and U87, U251 cells using real-time reverse transcription quantitative polymerase chain reaction (qRT-PCR) analysis. The effects of PAR5 on cell proliferation, migration and invasion were determined using in vitro assays. RNA immunoprecipitation (RIP) and RNA pull-down assays, as well as the evauation of the expression of various oncogenes were carried out to reveal the underlying mechanisms. We found that PAR5 was significantly downregulated in glioma tissues and cell lines. Furthermore, PAR5 expression was negatively correlated with tumor size, World Health Organization (WHO) grade and Karnofsky performance score (KPS). Patients with low PAR5 expression in tumors had a worse overall survival compared to those with higher expression. Finally, in vitro restoration of PAR5 expression inhibited human glioma cell proliferation, invasion and migration by binding to EZH2 and regulating oncogene expression. This finding may provide a therapeutic approach for the future treatment of glioma.
新出现的证据表明,长链非编码 RNA(lncRNA)可能参与调节肿瘤生物学的各个方面,并作为潜在的治疗靶点以及神经胶质瘤治疗中的新型生物标志物。本研究探讨了 lncRNA,Prader Willi/Angelman 区 RNA 5(PAR5;也称为 PWAR5)在神经胶质瘤中的作用及其在神经胶质瘤病例中的临床意义。采用实时逆转录定量聚合酶链反应(qRT-PCR)分析检测 PAR5 在临床样本和 U87、U251 细胞中的表达水平。采用体外实验检测 PAR5 对细胞增殖、迁移和侵袭的影响。进行 RNA 免疫沉淀(RIP)和 RNA 下拉实验以及评估各种癌基因的表达,以揭示潜在的机制。我们发现 PAR5 在神经胶质瘤组织和细胞系中显著下调。此外,PAR5 的表达与肿瘤大小、世界卫生组织(WHO)分级和卡氏功能状态评分(KPS)呈负相关。肿瘤中 PAR5 低表达的患者总生存期较高表达者差。最后,体外恢复 PAR5 的表达通过与 EZH2 结合并调节癌基因表达来抑制人神经胶质瘤细胞的增殖、侵袭和迁移。这一发现可能为神经胶质瘤的未来治疗提供一种治疗方法。