OBJECTIVES Chemoresistance is one of the major obstacles for gastric cancer (GC) treatment. Exosome-mediated transfer of circular RNAs (circRNAs) is associated with the drug-resistance in GC. Circ_0032821 has been reported as an oncogene in GC. This study is designed to explore the function and mechanism of Exosomal circ_0032821 in oxaliplatin (OXA) resistance of GC. RESULTS Circ_0032821 was highly expressed in OXA-resistant GC cells, and exosomes secreted by OXA-resistant GC cells. Moreover, circ_0032821-containing exosomes secreted by OXA-resistant GC cells could boost OXA resistance, proliferation, migration, and invasion in OXA-sensitive GC cells. The mechanical analysis discovered that circ_0032821 acted as a sponge of miR-515-5p to regulate SOX9 expression. Circ_0032821 silencing and OXA treatment repressed tumor growth in the GC mice model. CONCLUSIONS Exosomal circ_0032821 boosted OXA resistance of GC cells partly by the miR-515-5p/SOX9 axis, hinting a promising therapeutic target for GC treatment.

中文翻译：

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环状RNA circ_0032821通过miR-515-5p调节SOX9促进胃癌细胞的奥沙利铂（OXA）耐药

目的 化疗耐药是胃癌 (GC) 治疗的主要障碍之一。外泌体介导的环状 RNA (circRNA) 转移与 GC 中的耐药性有关。Circ_0032821 已被报道为 GC 中的致癌基因。本研究旨在探讨外泌体circ_0032821在GC奥沙利铂（OXA）耐药中的功能和机制。结果 Circ_0032821 在 OXA 抗性 GC 细胞和 OXA 抗性 GC 细胞分泌的外泌体中高表达。此外，OXA抗性GC细胞分泌的含有circ_0032821的外泌体可以增强OXA敏感GC细胞的OXA抗性、增殖、迁移和侵袭。力学分析发现 circ_0032821 作为 miR-515-5p 的海绵来调节 SOX9 的表达。Circ_0032821 沉默和 OXA 治疗抑制了 GC 小鼠模型中的肿瘤生长。