环状 RNA YAP1 通过调控 miR-367-5p/p27 轴抑制胃癌细胞的增殖和侵袭。
Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 axis.
机构信息
Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.
Nantong Institute of Liver Disease, Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Nantong University, Nantong, 226006, Jiangsu, China.
出版信息
Mol Cancer. 2018 Oct 18;17(1):151. doi: 10.1186/s12943-018-0902-1.
BACKGROUND
Circular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression.
METHODS
CircNet was used to screen potential circRNAs and validated circYAP1 expression levels in 17 GC tissues by quantitative real-time PCR (qRT-PCR) and another 80 paired GC tissues by FISH. CircYAP1 overexpression and knockdown experiments were conducted to assess the effects of circYAP1 in vitro and in vivo, and its molecular mechanism was demonstrated by RNA in vivo precipitation assays, western blotting, luciferase assay and rescue experiments.
RESULTS
CircYAP1 expression level was significantly lower in GC tissues than the adjacent normal tissues, and GC patients with circYAP1 low expression had shorter survival times as compared with those with circYAP1 high expression. Functionally, circYAP1 overexpression inhibited cell growth and invasion in vitro and in vivo, but its knockdown reversed these effects. Further analysis showed that circYAP1 sponged miR-367-5p to inhibit p27 expression and GC progression.
CONCLUSION
Our findings demonstrate that circYAP1 functions as a tumor suppressor in GC cells by targeting the miR-367-5p/p27 axis and may provide a prognostic indicator of survival in GC patients.
背景
环状 RNA（circRNAs）是一种新型的非编码 RNA，其在胃癌（GC）中的功能尚不清楚。最近的研究表明，circRNAs 在癌症发展和某些类型的病理反应中发挥重要作用，作为 microRNA（miRNA）海绵来调节基因表达。
方法
CircNet 用于筛选潜在的 circRNAs，并通过定量实时 PCR（qRT-PCR）验证 17 对 GC 组织中 circYAP1 的表达水平，通过 FISH 验证另外 80 对配对的 GC 组织中 circYAP1 的表达水平。进行 circYAP1 过表达和敲低实验，评估 circYAP1 在体外和体内的作用，并通过 RNA 体内沉淀实验、western blot 分析、荧光素酶测定和挽救实验证明其分子机制。
结果
GC 组织中 circYAP1 的表达水平明显低于相邻正常组织，circYAP1 低表达的 GC 患者的生存时间明显短于 circYAP1 高表达的患者。功能上，circYAP1 过表达抑制了体外和体内的细胞生长和侵袭，但它的敲低逆转了这些效应。进一步分析表明，circYAP1 作为 miR-367-5p 的海绵，抑制了 p27 的表达，从而抑制了 GC 的进展。
结论
我们的研究结果表明，circYAP1 通过靶向 miR-367-5p/p27 轴在 GC 细胞中发挥肿瘤抑制作用，可能为 GC 患者的生存提供一个预后指标。
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