SAT-315 CircVPS13c Promotes Tumor Growth and Invasiveness in Pituitary Adenoma by Downregulating IFITM1

Background and objectives Invasive nonfunctioning pituitary adenoma (NFPA) remains the major cause of hypopituitarism and infertility. Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression in a wide range of tumors. The present study was designed to explore the role of circRNAs in proliferation and invasion of NFPAs. Methods The expression profile of circRNAs was compared with circRNA array between NFPA (n=10) and normal pituitary tissues (n=4), invasive (n=5) and noninvasive (n=5) NFPA samples. A total of 249 circRNAs were shown to be significantly upregulated in human invasive NFPA tissues, comparing to the noninvasive ones. CircVPS13C was identified for further study, whose oncogenic effect were explored with in vitro and in vivo experiments. Results CircVPS13C was markedly upregulated in NFPA samples and positively correlated with NFPA invasiveness. Silencing of circVPS13C effectively suppressed NFPA cell proliferation, invasiveness and promoted apoptosis, in vitro, and suppressed tumor growth, in vivo. The oncogenic effects were significantly enhanced when circVPS13C was overexpressed. By whole exome sequencing, interferon induced transmembrane protein 1 (IFITM1) was found significantly increased in cells with circVPS13C knockout. Decreased level of IFITM1 protein was confirmed in NFPAs samples, and negatively correlated with the level of circVPS13C and tumor invasiveness. Upregulation of IFITM1 could partly reverse the effect of IFITM1 on tumor cells, and IFITM1 downregulating enhanced the oncogenic effect of circVPS13C. CHIRP analysis suggested that circVPS13C may inhibit the IFITM1 transcription by competitively binding the RNA-associated proteins. Conclusions CircVPS13C promotes NFPA growth and invasiveness by regulating tumor suppressor IFITM1, revealing a therapeutic target in preventing the tumorigenesis of NFPA.