Xie Zuochang, Li Xiaojian, Chen Hua, Zeng Ailiang, Shi Yan, Tang Yong
Department of Neurosurgery, The First People's Hospital of Tianmen City Tianmen 431700, Hubei, China.
Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University Nanjing 210006, Jiangsu, China.
Am J Transl Res. 2019 Aug 15;11(8):4922-4934. eCollection 2019.
Long non-coding RNAs (lncRNAs) have great value in research on tumour targeted therapy, including for glioma. In the present study, we investigated the role of the lncRNA deleted in lymphocytic leukaemia 2 (lncRNA-DLEU2) in glioma. First, we found that lncRNA-DLEU2 is highly expressed in glioma tissues and cell lines. Next, experiments in cells showed that lncRNA-DLEU2 knockdown inhibited, whereas lncRNA-DLEU2 overexpression promoted, the clone formation, migration and invasion of glioma cells. A luciferase reporter assay and an RNA immunoprecipitation assay demonstrated that lncRNA-DLEU2 acts as a sponge for miR-186-5p in glioma cells. Further, studies suggested that miR-186-5p inhibits the expression of PDK3, which is an oncogene in glioma. Moreover, with rescue experiments, we demonstrated that lncRNA-DLEU2 regulates the expression of PDK3 and the progression of glioma in a miR-186-5p-dependent manner. Finally, we also showed that lncRNA-DLEU2 promotes glioma growth in a manner that is related to miR-186-5p and PDK3 . In conclusion, our study reported for the first time that lncRNA-DLEU2 promotes glioma progression by targeting the miR-186-5p/PDK3 axis. These findings provide novel strategies for the gene therapy treatment of glioma.
长链非编码RNA(lncRNAs)在肿瘤靶向治疗研究中具有重要价值,包括对神经胶质瘤的研究。在本研究中,我们调查了淋巴细胞白血病2中缺失的lncRNA(lncRNA-DLEU2)在神经胶质瘤中的作用。首先,我们发现lncRNA-DLEU2在神经胶质瘤组织和细胞系中高表达。接下来,细胞实验表明,敲低lncRNA-DLEU2可抑制神经胶质瘤细胞的克隆形成、迁移和侵袭,而lncRNA-DLEU2过表达则促进这些过程。荧光素酶报告基因检测和RNA免疫沉淀检测表明,lncRNA-DLEU2在神经胶质瘤细胞中充当miR-186-5p的海绵。此外,研究表明miR-186-5p抑制PDK3的表达,而PDK3是神经胶质瘤中的一种癌基因。而且,通过挽救实验,我们证明lncRNA-DLEU2以miR-186-5p依赖的方式调节PDK3的表达和神经胶质瘤的进展。最后,我们还表明lncRNA-DLEU2以与miR-186-5p和PDK3相关的方式促进神经胶质瘤生长。总之,我们的研究首次报道lncRNA-DLEU2通过靶向miR-186-5p/PDK3轴促进神经胶质瘤进展。这些发现为神经胶质瘤的基因治疗提供了新策略。