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Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer

Oncogene volume 38, pages 6985–7001 (2019)Cite this article

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Abstract

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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Acknowledgements

This work was partially supported by the National Natural Science Foundation of China (81572362); the National Natural Science Foundation Project of International Cooperation (NSFC-NIH, 81361120398); the Primary Research & Development Plan of Jiangsu Province (BE2016786); the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU; the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, JX10231801); 333 Project of Jiangsu Province (BRA2015474); Jiangsu Key Medical Discipline (General Surgery) (ZDXKA2016005); and Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University.

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  1. These authors contributed equally: Sen Wang, Xing Zhang, Zheng Li

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  1. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China

    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, Jiacheng Cao, Penghui Xu, Diancai Zhang, Hao Xu & Zekuan Xu

  2. Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China

    Jie Chen & Yangjun Wu

  3. Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China

    Zekuan Xu

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Wang, S., Zhang, X., Li, Z. et al. Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer. Oncogene 38, 6985–7001 (2019). https://doi.org/10.1038/s41388-019-0933-0

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