Circ-EZH2 knockdown reverses DDAH1 and CBX3-mediated cell growth and invasion in glioma through miR-1265 sponge activity
Circ-EZH2 knockdown reverses DDAH1 and CBX3-mediated cell growth and invasion in glioma through miR-1265 sponge activity
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DOI：
10.1016/j.gene.2019.144196
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发表时间：
2020-02-05
期刊：
影响因子：
3.5
通讯作者：
Chen, Dagang
中科院分区：
文献类型：
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作者：
Gao, Fengquan;Du, Yan;Chen, Dagang
越来越多的证据表明，环状RNA（circular RNA，circRNA）在多种肿瘤中发挥着重要作用。然而，其在胶质瘤中的详细调控机制尚未完全了解。在这项研究中，一种新的circRNA，circ-EZH 2，的功能作用进行了研究，细胞计数试剂盒-8（CCK-8），集落形成，流式细胞术，和transwell实验。通过生物信息学分析、实时荧光定量PCR（qRT-PCR）、Western blot和双荧光素酶报告基因分析，探讨circ-EZH 2的调控机制。我们发现circ-EZH 2在胶质瘤组织和细胞系中过表达。进一步研究发现，circ-EZH 2的异位表达可显著促进细胞的生长、迁移和侵袭，但抑制细胞凋亡。相比之下，circ-EZH 2的沉默诱导了相反的效果。此外，我们发现circ-EZH 2充当miR-1265的miRNA海绵，以释放其对DDAH 1和CBX 3的抑制。拯救测定进一步揭示了circ-EZH 2的致癌功能部分依赖于其对DDAH 1和CBX 3的调节。本研究揭示了胶质瘤中一条新的分子通路，为胶质瘤的治疗提供了新的思路。
Accumulating evidence has indicated the important roles of circular RNAs (circRNAs) in different tumors. However, their detailed regulatory mechanisms in glioma are not fully understood. In this study, the functional role of a novel circRNA, circ-EZH2, was investigated by cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell experiments. The regulatory mechanism of circ-EZH2 was explored by bioinformatics analysis, quantitative real-time PCR (qRT-PCR), Western blot and dual-luciferase reporter assay. We identified that circ-EZH2 was overexpressed in glioma tissues and cell lines. Further studies revealed that ectopic expression of circ-EZH2 significantly promoted cell growth, migration and invasion but inhibited cell apoptosis. By contrast, silencing of circ-EZH2 induced the opposite effects. Additionally, we found circ-EZH2 served as a miRNA sponge for miR-1265 to release its suppression on DDAH1 and CBX3. Rescue assays further revealed that the oncogenic function of circ-EZH2 was partly dependent on its modulation of DDAH1 and CBX3. Our study unraveled a novel molecular pathway in glioma and may provide a new perspective for the treatment of glioma.