Ma Ruiqiong, Ye Xue, Cheng Hongyan, Cui Heng, Chang Xiaohong
Department of Obstetrics and Gynecology, Peking University People's Hospital Beijing 100044, China.
Center of Gynecologic Oncology, Peking University People's Hospital Beijing 100044, China.
Am J Transl Res. 2021 Mar 15;13(3):1125-1139. eCollection 2021.
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.
最近的研究表明,外泌体参与肿瘤进展过程中的细胞间通讯。环状RNA(circRNAs)可以被包装到外泌体中进行细胞外通讯,然而,外泌体circRNAs在具有高转移潜能的上皮性卵巢癌(EOC)细胞中的可能作用鲜有研究。在本研究中,我们从高转移性卵巢癌SKOV3.ip细胞中鉴定出外泌体circRNA051239,随后通过qRT-PCR分析EOC组织以及血浆和细胞来源的外泌体中circRNA051239的水平。采用多种体外试验观察高转移性卵巢癌SKOV3.ip细胞来源的外泌体circRNA051239对低转移性卵巢癌SKOV3细胞的影响。进一步利用生物信息学分析和荧光素酶活性测定来证实circRNA051239、miR-509-5p和PRSS3之间的关系。结果显示,EOC患者组织和血浆外泌体中circRNA051239表达增加。此外,si-circRNA051239-Exo(来自circRNA051239敲低的SKOV3.ip细胞的外泌体)抑制了SKOV3细胞的增殖、迁移和侵袭。机制上,circRNA051239通过海绵吸附miR-509-5p作为竞争性内源RNA(ceRNA)来促进PRSS3表达。高转移性卵巢癌SKOV3.ip细胞来源的外泌体circRNA051239促进了低转移性卵巢癌SKOV3细胞的进展。总的来说,这些结果表明,高转移性EOC细胞可以通过外泌体circRNA051239将这种潜能赋予低转移潜能的细胞,导致受体细胞的增殖、迁移和侵袭能力增强。