Objective. Cancer-derived exosomes can facilitate drug resistance in cervical cancer. However, the mechanisms remain elusive. Herein, we observed the roles of exosomal miR-651 in cisplatin resistance of cervical cancer. Methods. Circulating miR-651 was detected in cervical cancer and healthy individuals. The diagnostic efficacy was determined. When transfected with miR-651 mimics, cisplatin resistance, apoptosis, and proliferation were assessed. The cancer-derived exosomes were separated and identified. We observed the uptake of PKH67-labeled exosomes by HeLa/S cells. After coculture with exosomes secreted by HeLa/S or HeLa/DDP cells, malignant behaviors were examined in HeLa/S cells. The interactions between ATG3 and miR-651 were validated by dual luciferase report. Biological behaviors were investigated for HeLa/S cells cocultured with exosomes secreted by miR-651 mimic-transfected HeLa/DDP cells. Results. Downregulated circulating miR-651 was found in cancer subjects than healthy individuals. It possessed high sensitivity and accuracy in diagnosing cervical cancer (). Lower miR-651 expression was confirmed in HeLa/DDP than HeLa/S cells. Forced miR-651 lessened cisplatin resistance and proliferation and elevated apoptosis in HeLa cells. ATG3 was a direct target of miR-651. The exosomes isolated from HeLa cells were rich in CD63, CD9, and CD81 proteins, thereby identifying the isolated exosomes. Exosomes secreted by HeLa/DDP cells can be absorbed by HeLa/S cells. When being cocultured with exosomes secreted by HeLa/DDP cells, malignant behaviors of HeLa/S cells were enhanced, which were ameliorated by miR-651 mimic exosomes. Conclusion. Our findings showed that cancer-derived exosomal miR-651 restrained cisplatin resistance and directly targeted ATG3, indicating that exosomal miR-651 could be a therapeutic agent.

中文翻译：

---

癌症衍生的外泌体 miR-651 作为诊断标志物抑制顺铂耐药并直接靶向 ATG3 治疗宫颈癌

客观。癌症衍生的外泌体可以促进宫颈癌的耐药性。然而，这些机制仍然难以捉摸。在此，我们观察了外泌体 miR-651 在宫颈癌顺铂耐药中的作用。方法. 在宫颈癌和健康个体中检测到循环 miR-651。确定诊断效力。当用 miR-651 模拟物转染时，评估了顺铂抗性、细胞凋亡和增殖。分离和鉴定癌症衍生的外泌体。我们观察到 HeLa/S 细胞对 PKH67 标记的外泌体的摄取。与 HeLa/S 或 HeLa/DDP 细胞分泌的外泌体共培养后，检测 HeLa/S 细胞的恶性行为。双荧光素酶报告验证了 ATG3 和 miR-651 之间的相互作用。研究了与转染 miR-651 模拟物的 HeLa/DDP 细胞分泌的外泌体共培养的 HeLa/S 细胞的生物学行为。结果. 与健康个体相比，在癌症受试者中发现了下调的循环 miR-651。对宫颈癌的诊断具有较高的敏感性和准确性（）。证实 HeLa/DDP 中 miR-651 表达低于 HeLa/S 细胞。强制 miR-651 可降低 HeLa 细胞的顺铂耐药性和增殖，并提高细胞凋亡。ATG3 是 miR-651 的直接靶标。从 HeLa 细胞中分离的外泌体富含 CD63、CD9 和 CD81 蛋白，从而鉴定了分离的外泌体。HeLa/DDP 细胞分泌的外泌体可被 HeLa/S 细胞吸收。与 HeLa/DDP 细胞分泌的外泌体共培养时，HeLa/S 细胞的恶性行为得到增强，miR-651 模拟外泌体改善了这些行为。结论。我们的研究结果表明，癌症衍生的外泌体 miR-651 抑制了顺铂耐药并直接靶向 ATG3，表明外泌体 miR-651 可能是一种治疗剂。