Abstract

Exosomes , which are small extracellular vesicles, have been unveiled to carry circular RNAs (circRNAs). CircRNA paired-related homeobox 1 ( circPRRX1 ) can be transferred by exosomes derived from gastric cancer cells. Here, we investigated the activity and mechanism of exosomal circPRRX1 in gastric tumorigenesis and radiation sensitivity. CircPRRX1 , microRNA (miR)-596, and NF-κB activating protein (NKAP) were quantified by quantitative real-time PCR and immunoblotting. Cell proliferation, motility, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and transwell assays, respectively. Cell colony formation and survival were assessed by colony formation assays. Dual-luciferase reporter assays were performed to verify the direct relationship between miR-596 and circPRRX1 or NKAP . In-vivo xenograft studies were used to evaluate the role of exosomal circPRRX1 in tumor growth. Our data showed that circPRRX1 expression was elevated in human gastric cancer , and circPRRX1 could be transferred by exosomes from gastric cancer cells. Exosomal circPRRX1 affected cell proliferation, motility, invasion, and radiation sensitivity in vitro and tumor growth in vivo . Mechanistically, circPRRX1 directly regulated miR-596 expression, and exosomal circPRRX1 affected cell biological functions at least in part through miR-596 . NKAP was identified as a direct target and functionally downstream effector of miR-596 . Exosomal circPRRX1 modulated NKAP expression by acting as a competing endogenous RNA (ceRNA) for miR-596 . Our findings suggest a new mechanism, the exosomal circPRRX1 / miR-596 / NKAP ceRNA crosstalk , in regulating gastric tumorigenesis and radiation sensitivity.