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环状非编码 RNA NT5E 通过吸附 miR-422a 促进脑胶质母细胞瘤发生。

CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis.

机构信息

Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, China.

Department of Neurosurgery, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, China.

出版信息

Cancer Res. 2018 Sep 1;78(17):4812-4825. doi: 10.1158/0008-5472.CAN-18-0532. Epub 2018 Jul 2.

Abstract

Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a-downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis. Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. .

摘要

环状 RNA 和长非编码 RNA 可作为有效的 miRNA 海绵,调节真核生物中的基因表达。然而,胶质母细胞瘤中功能性 miRNA 的海绵仍知之甚少。在这里,我们鉴定出了一小部分circRNA 和 lncRNA,它们在 miR-422a 下调的胶质母细胞瘤组织中特异性增加。我们描述了一种新型的环状 RNA,命名为 circNT5E,它由 ADARB2 结合到环状 RNA 形成内含子侧翼的位点来调控。我们假设 circNT5E 可能在胶质母细胞瘤发生中作为 miR-422a 的海绵。circNT5E 控制多种病理过程,包括细胞增殖、迁移和侵袭。circNT5E 直接结合 miR-422a 并抑制 miR-422a 活性。此外,circNT5E 被观察到还能吸附其他 miRNA,表现出胶质母细胞瘤中的肿瘤抑制子样特征。总之,这些发现强调了环状 RNA 在胶质母细胞瘤发生中的新型致癌功能。circRNA/lncRNA/mRNA 的微阵列分析鉴定 circNT5E 为一种致癌环状 RNA 和 miR-422a 的海绵。

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