Department of Gastroenterology, Weifang People's Hospital, No. 151, Guangwen Street, Kuiwen District, Weifang, 261041, Shandong, China.
Department of Internal Medicine, Changle County Tangwu Town Hospital, Weifang, Shandong, China.
Biotechnol Lett. 2021 Feb;43(2):339-351. doi: 10.1007/s10529-020-03036-3. Epub 2020 Oct 29.
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.
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.
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.
化疗耐药性是胃癌（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 中奥沙利铂（OXA）耐药中的功能和机制。
Circ_0032821 在 OXA 耐药 GC 细胞和 OXA 耐药 GC 细胞分泌的外泌体中高表达。此外，OXA 耐药 GC 细胞分泌的含有 circ_0032821 的外泌体可增强 OXA 敏感 GC 细胞中的 OXA 耐药性、增殖、迁移和侵袭。机制分析发现 circ_0032821 作为 miR-515-5p 的海绵调节 SOX9 表达。Circ_0032821 沉默和 OXA 处理抑制了 GC 小鼠模型中的肿瘤生长。
外泌体 circ_0032821 通过 miR-515-5p/SOX9 轴增强 GC 细胞的 OXA 耐药性，提示其可能成为 GC 治疗的有前途的治疗靶点。
