以顺铂为基础的化疗是胃癌（GC）的基本治疗方式之一。对顺铂的化学耐药性是一个巨大的临床挑战，其潜在机制仍知之甚少。环状RNA（circRNA）参与多种人类恶性肿瘤的病理生理学。通过高通量测序确定circRNA在GC组织和顺铂耐药GC细胞中的差异表达谱。利用定量实时聚合酶链反应和荧光原位杂交证实GC组织中circ_0008315的失调。为了评估 circ_0008315 在 GC 中的预后意义，我们使用了 Kaplan-Meier 图。通过肿瘤球形成实验验证了耐药GC细胞的自我更新能力。构建GC类器官模拟肿瘤微环境，验证circ_0008315在胃癌顺铂耐药中的功能。使用源自患者的异种移植模型进行体内评估。采用双荧光素酶报告基因、RNA免疫沉淀和miRNA Pull-down实验来研究circ_0008315在GC中的分子机制。我们发现一种新的circRNA hsa_circ_0008315在GC和顺铂耐药的GC细胞中表达上调。在顺铂耐药的 GC 类器官模型中也观察到 circ_0008315 升高。 circ_0008315 的高表达预示着 GC 患者的不利生存结果。 circ_0008315 表达下调可抑制体外和体内 GC 细胞的增殖、迁移和上皮间质转化。减少顺铂耐药 GC 类器官模型中 circ_0008315 的表达可逆转顺铂耐药。从机制上讲，circ_0008315通过miR-3666/CPEB4信号通路调节GC的干细胞特性，从而促进顺铂耐药和GC恶性进展。此外，我们还开发了针对circ_0008315的PLGA-PEG纳米颗粒，该纳米颗粒可以有效抑制GC增殖和顺铂耐药。Circ_0008315加剧GC进展和顺铂耐药，可作为预后预测因子。 Circ_0008315 可能作为 GC 治疗的一个有前途的纳米治疗靶点。© 2024。作者。

Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies.High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC.We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance.Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.© 2024. The Author(s).