Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR-515-5p
Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR-515-5p
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DOI：
10.1007/s10529-020-03036-3
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发表时间：
2020-10-29
影响因子：
2.7
通讯作者：
Jiang, Bing
中科院分区：
文献类型：
--
作者：
Zhong, Yanmei;Wang, Dan;Jiang, Bing
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 的耐药性相关。据报道，Circ_0032821 是 GC 中的癌基因。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 耐药 GC 细胞中高表达，并且 OXA 耐药 GC 细胞分泌的外泌体。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 治疗可抑制 GC 小鼠模型中的肿瘤生长。结论 外泌体 circ_0032821 部分通过 miR-515-5p/SOX9 轴增强 GC 细胞的 OXA 耐药性，暗示着 GC 治疗的一个有前途的治疗靶点。
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.