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新型环状 RNA circNF1 作为分子海绵,通过吸收 miR-16 促进胃癌。

Novel circular RNA circNF1 acts as a molecular sponge, promoting gastric cancer by absorbing miR-16.

机构信息

Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Division of Gastroenterology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

出版信息

Endocr Relat Cancer. 2019 Mar;26(3):265-277. doi: 10.1530/ERC-18-0478.

Abstract

Circular RNAs (circRNAs) are a new class of RNA involved in multiple human malignancies. However, limited information exists regarding the involvement of circRNAs in gastric carcinoma (GC). Therefore, we sought to identify novel circRNAs, their functions and mechanisms in gastric carcinogenesis. We analyzed next-generation RNA sequencing data from GC tissues and cell lines, identifying 75,201 candidate circRNAs. Among these, we focused on one novel circRNA, circNF1 , which was upregulated in GC tissues and cell lines. Loss- and gain-of-function studies demonstrated that circNF1 significantly promotes cell proliferation. Furthermore, luciferase reporter assays showed that circNF1 binds to miR-16, thereby derepressing its downstream target mRNAs, MAP7 and AKT3. Targeted silencing or overexpression of circNF1 had no effect on levels of its linear RNA counterpart, NF1. Taken together, these results suggest that circNF1 acts as a novel oncogenic circRNA in GC by functioning as a miR-16 sponge.

摘要

环状 RNA(circRNAs)是一类参与多种人类恶性肿瘤的新型 RNA。然而,关于环状 RNA 参与胃癌(GC)的信息有限。因此,我们试图鉴定新型环状 RNA 及其在胃癌发生中的功能和机制。我们分析了来自 GC 组织和细胞系的下一代 RNA 测序数据,确定了 75201 个候选环状 RNA。在这些环状 RNA 中,我们重点关注了一个新型环状 RNA circNF1,其在 GC 组织和细胞系中上调。敲低和过表达研究表明,circNF1 可显著促进细胞增殖。此外,荧光素酶报告基因检测表明 circNF1 可与 miR-16 结合,从而解除其下游靶基因 mRNAs MAP7 和 AKT3 的抑制。靶向沉默或过表达 circNF1 对其线性 RNA 对应物 NF1 的水平没有影响。总之,这些结果表明 circNF1 作为一种新型致癌环状 RNA,通过作为 miR-16 的海绵发挥作用,在 GC 中发挥作用。

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