Cancer-derived exosomes carrying tumor-derived molecules such as miRNAs and proteins related to various phenotypes have been detected in both the bloodstream and other biofluids of patients with different cancers. Thus, our main purpose here was to determine the role of the exosomal microRNA-454 (miR-454) derived by MDA-MB-231 in self-renewal of cancer stem cells (CSCs) in ovarian cancer (OC). Extraction of MDA-MB-231 cells-derived exosomes (231-derived exosomes) was conducted to treat CD44+/CD133+ SKOV3 and CoC1 cells to observe cell growth and stemness. Next, the differentially expressed miRNAs in SKOV3 cells after exosome treatment were filtered using microarray analysis. Subsequently, the cell viability was detected after reducing the exosomal miR-454 and the addition of a Wnt pathway inhibitor C59. Finally, the pro-tumorigenic function of exosomes on OC cells was investigated. After co-culture with 231-derived exosomes, the stemness of CSCs were promoted. Subsequently, the reduction of exosomal miR-454 weakened the roles of exosomes on cell stemness. Proline-rich transmembrane protein 2 (PRRT2) was substantiated as a target gene of miR-454 in SKOV3 and CoC1 cells. C59 reversed the repressive role of exosomes in stemness of CSCs. When being evaluated in a mouse model, exosomal miR-454 led to an efficacious effect in suppressing the tumor weight and volume . Altogether, 231-derived exosomes carrying miR-454 disrupted the Wnt pathway by targeting PRRT2, thereby promoting CSC stemness and OC cell growth .

中文翻译：

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乳腺癌细胞外泌体释放 microRNA-454 通过卵巢癌中的 PRRT2/Wnt 轴维持癌症干细胞的生物学特性

在不同癌症患者的血液和其他生物体液中都检测到了携带肿瘤衍生分子（例如 miRNA 和与各种表型相关的蛋白质）的癌症衍生外泌体。因此，我们的主要目的是确定 MDA-MB-231 衍生的外泌体 microRNA-454 (miR-454) 在卵巢癌 (OC) 中癌症干细胞 (CSC) 自我更新中的作用。提取MDA-MB-231细胞来源的外泌体（231来源的外泌体）处理CD44+/CD133+SKOV3和CoC1细胞，观察细胞生长和干性。接下来，使用微阵列分析过滤外泌体处理后SKOV3细胞中差异表达的miRNA。随后，减少外泌体miR-454并添加Wnt通路抑制剂C59后检测细胞活力。最后，研究了外泌体对 OC 细胞的促肿瘤作用。与231来源的外泌体共培养后，CSC的干性得到提升。随后，外泌体miR-454的减少削弱了外泌体对细胞干性的作用。富含脯氨酸的跨膜蛋白 2 (PRRT2) 被证实是 SKOV3 和 CoC1 细胞中 miR-454 的靶基因。 C59 逆转了外泌体对 CSC 干性的抑制作用。在小鼠模型中进行评估时，外泌体 miR-454 在抑制肿瘤重量和体积方面发挥了有效作用。总之，携带 miR-454 的 231 衍生外泌体通过靶向 PRRT2 破坏了 Wnt 通路，从而促进 CSC 干细胞性和 OC 细胞生长。