生物
环状RNA
基因沉默
核糖核酸
癌症研究
小RNA
癌症
基因
转移
竞争性内源性RNA
下调和上调
长非编码RNA
癌变
分子生物学
遗传学
作者
Sen Wang,Xing Zhang,Zheng Li,Weizhi Wang,Bowen Li,Xiaoxu Huang,Guangli Sun,Jianghao Xu,Qing Li,Zhipeng Xu,Yiwen Xia,Lu Wang,Qiang Zhang,Qiang Li,Lu Zhang,Jie Chen,Yangjun Wu,Jiacheng Cao,Penghui Xu,Diancai Zhang,Hao Xu,Zekuan Xu
出处
期刊:Oncogene
[Springer Nature]
日期:2019-08-13
卷期号:38 (44): 6985-7001
被引量:71
标识
DOI:10.1038/s41388-019-0933-0
摘要
The prognosis after curative resection of gastric cancer (GC) remains unsatisfactory, and thus, the development of treatments involving alternative molecular and genetic targets is critical. Circular RNAs (circRNAs), which are newly discovered molecules with key roles in the non-coding RNA network, have been identified as critical regulators in various cancers. Here, we aimed to determine the circRNA expression profile and to investigate the functional and prognostic significance of circRNA in GC. Using next-generation sequencing profiling, we first characterized an abundant circRNA in GC, hsa_circ_0008549, derived from the OSBPL10 gene and named it circOSBPL10. The expression of circOSBPL10 was found to be upregulated in GC tissues by quantitative RT-PCR, and silencing of circOSBPL10 significantly inhibited GC cell growth, migration, and invasion in multiple experiments. We further confirmed that miR-136-5p is a downstream target of circOSBPL10 using RNA pull-down and luciferase reporter assays. Rescue experiments confirmed that circOSBPL10 regulates biological functions in GC cells via a circOSBPL10-miR-136-5p-WNT2 axis. In vivo experiments showed that circOSBPL10 promotes tumor growth and metastasis in mice. Furthermore, the level of circOSBPL10 was observed to be a prognostic marker of the overall survival and disease-free survival of patients with GC. Taken together, our findings reveal that circOSBPL10 may serve as a new proliferation factor and prognostic marker in GC.
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