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

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.