CircMORC1 downregulated in plasma EVs promotes gastric cancer cell proliferation and invasion via miR-103a-1-5p sponging.

BACKGROUND: Gastric cancer (GC) is the fourth most common cause of cancer death and has the fifth highest incidence of cancer worldwide. Circular RNAs (circRNAs) have emerged as essential regulators of tumorigenesis and cancer progression. However, the underlying regulatory mechanisms and their roles as diagnostic biomarkers have yet to be well elucidated in GC. METHODS: In this study, we implemented genome-wide sequencing to identify circRNAs whose expression in plasma extracellular vesicles (EVs) significantly changed. Functional experiments were performed to assess its effect on the proliferation, viability, migration and apoptosis of GC cell lines. Luciferase reporter and RNA pull-down assays were used to validate their combinations. Finally, RNA-Seq and RT-qPCR were used to identify the downstream regulatory pathway involved. RESULTS: We found that the circRNA of MORC family CW-type zinc finger 1 gene (circMORC1) was decreased in the plasma EVs of GC patients but increase in GC cells. In vivo, circMORC1 promoted proliferation, viability, and migration and inhibited apoptosis in AGS and SGC-7901 GC cell lines. CircMORC1 was found to bind to miR-103a-1-5p, which is essential for the regulation of phenotypes. In addition, the Wnt pathway was found to be the downstream regulatory pathway of circMORC1 through a miR-103a-1-5p sponge. CONCLUSIONS: Our results shed light on circMORC1 promotes the proliferation of gastric cancer cells, as a RNA sponge of miR-103a-1-5p and counteracted the down-regulation of Wnt signaling function of miR-103a-1-5p. Revealed a novel mechanism by which circMORC1 regulates tumorigenesis in gastric cancer and provided a new biomarker for GC diagnosis and prognosis.