Background: The development of drug resistance leads many NPC patients to experience disease relapse following the completion of chemotherapy. It is thus essential that the mechanistic basis for such chemoresistance be clarified in an effort to identify approaches to sensitizing NPC tumors to treatment with cisplatin and related agents.
Methods: A qRT-PCR approach was used to measure the expression of circNRIP1 in NPC, while luciferase assays were used to identify interactions with downstream targets of circNRIP1 activity including miR-515-5p and IL-25. CCK8 assays were also utilized to detect IC50 values for cisplatin and 5-Fu.
Results: The expression of circNRIP1 was significantly increased in the serum of chemoresistant NPC patients. At a functional level, we determined that circNRIP1 is able to sequester miR-515-5p, thereby inhibiting its ability to post-transcriptionally suppress IL-25 expression. We observed a significant negative correlation between the expression of miR-515-5p and circNRIP1 in serum samples from chemoresistant NPC patients, consistent with a functional interaction between these two factors. We further found that 5-Fu and CDDP IC50 values in NPC cells in which circNRIP1 had been knocked down were restored following miR-515-5p inhibitor transfection. Similarly, changes in these IC50 values were reversed in NPC cells transfected with miR-515-5p mimics following the overexpression of IL-25 in these same cells.
Conclusion: These data highlight the circNRIP1/miR-515-5p/IL-25 as a novel regulator of 5-Fu and cisplatin resistance in NPC, suggesting that this pathway may be amenable to therapeutic targeting as an approach to treating this cancer type.



中文翻译：

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CircNRIP1 调节 miR-515-5p/IL-25 轴以控制鼻咽癌的 5-Fu 和顺铂耐药

背景：耐药性的发展导致许多 NPC 患者在完成化疗后出现疾病复发。因此，必须阐明这种化学抗性的机制基础，以努力确定使 NPC 肿瘤对顺铂和相关药物治疗敏感的方法。
方法： qRT-PCR 方法用于测量 circNRIP1 在 NPC 中的表达，而荧光素酶测定用于识别与 circNRIP1 活性下游靶标（包括 miR-515-5p 和 IL-25）的相互作用。CCK8 测定也用于检测顺铂和 5-Fu 的 IC50 值。
结果：circNRIP1在化疗耐药NPC患者血清中的表达显着增加。在功能水平上，我们确定 circNRIP1 能够隔离 miR-515-5p，从而抑制其转录后抑制 IL-25 表达的能力。我们观察到化疗耐药 NPC 患者血清样本中 miR-515-5p 和 circNRIP1 的表达呈显着负相关，这与这两个因素之间的功能相互作用一致。我们进一步发现，在转染 miR-515-5p 抑制剂后，敲除 circNRIP1 的 NPC 细胞中的 5-Fu 和 CDDP IC50 值恢复。类似地，在这些相同细胞中过表达 IL-25 后，在用 miR-515-5p 模拟物转染的 NPC 细胞中，这些 IC50 值的变化被逆转。
结论：这些数据强调了 circNRIP1/miR-515-5p/IL-25 作为 NPC 中 5-Fu 和顺铂耐药的新型调节因子，表明该途径可能适合作为治疗这种癌症类型的治疗靶向方法。