Tumor-derived exosomal circRNA051239 promotes proliferation and migration of epithelial ovarian cancer

Am J Transl Res. 2021 Mar 15;13(3):1125-1139. eCollection 2021.

Abstract

Recent studies have shown the involvement of exosomes in intercellular communication during tumor progression. Circular RNAs (circRNAs) can be packaged into exosomes for extracellular communication, however, the possible effects of exosomal circRNAs in epithelial ovarian cancer (EOC) cells with high metastatic potential have been rarely studied. In this study, we identified exosomal circRNA051239 from high-metastatic ovarian cancer SKOV3.ip cells and subsequently analyzed circRNA051239 levels in both EOC tissues and exosomes derived from plasma and cells by qRT-PCR. A variety of in vitro assays were employed to observe the effects of exosomal circRNA051239 derived from high-metastatic ovarian cancer SKOV3.ip cells on low-metastatic ovarian cancer SKOV3 cells. Bioinformatics analysis and luciferase activity assays were further utilized to confirm the relationship between circRNA051239, miR-509-5p and PRSS3. As a result, circRNA051239 expression was increased in tissues and plasma exosomes from EOC patients. Moreover, si-circRNA051239-Exo (exosomes derived from circRNA051239 knockdown SKOV3.ip cells) inhibited the proliferation, migration as well as invasion of SKOV3 cells. Mechanistically, circRNA051239 functioned as a competitive endogenous RNA (ceRNA) by sponging miR-509-5p to facilitate PRSS3 expression. Exosomal circRNA051239 derived from high-metastatic ovarian cancer SKOV3.ip cells promoted the progression of low-metastatic ovarian cancer SKOV3 cells. Collectively, these outcomes implicated that higher metastatic EOC cells can confer this potential to lower metastatic potential via exosomal circRNA051239, causing enhanced proliferative, migratory and invasive capacities in recipient cells.

Keywords: Epithelial ovarian cancer; circRNA051239; exosomes; metastasis.