由于其复杂性和多样性，BCR-ABL1 独立的伊马替尼耐药尚无有效的治疗方法。我们之前报道过 CDH13 癌基因在不依赖 BCR-ABL1 的耐药 CML 细胞系中低水平表达。然而，其对 CML 耐药细胞的影响和机制仍不清楚。本研究探讨了基于saRNA的CDH13激活对CML中不依赖于BCR-ABL1的伊马替尼耐药的影响及其潜在机制，并提出了克服伊马替尼耐药的独特治疗方法。具体来说，本研究证明，使用 DSIR（小干扰 RNA 设计器）网站工具，可以生成靶向 CDH13 启动子区域的 saRNA，并使用 qPCR 和蛋白质印迹进行验证。在预测的序列中，C2和C3有效提高CDH13 mRNA和蛋白表达，并抑制细胞的相对活力和形成克隆的能力。在促进K562-IMR细胞中CDH13的表达后，它抑制NF-κB信号通路并诱导伊马替尼耐药的CML细胞凋亡。还观察到 LNP-saRNA (C3) 可以限制体内 K562-IMR 细胞的生长。综上所述，saRNA激活CDH13表达，通过抑制NF-κB信号通路促进细胞凋亡，从而克服CML患者对伊马替尼的不依赖于BCR-ABL1的耐药性。© 2024。作者。

BCR-ABL1-independent resistance to imatinib has no effective treatment due to its complexity and diversity. We previously reported that the CDH13 oncogene was expressed at low levels in BCR-ABL1-independent resistant CML cell lines. However, its effects on CML resistant cells and mechanisms remain unknown. This study investigated the effects of saRNA-based CDH13 activation on BCR-ABL1-independent imatinib resistance in CML and its underlying mechanism, and proposes a unique treatment method to overcome imatinib resistance. Specifically, this study demonstrated that using the DSIR (Designer of Small Interfering RNA) website tool, saRNAs targeting the CDH13 promoter region were generated and validated using qPCR and western blotting. Among the predicted sequences, C2 and C3 efficiently elevated CDH13 mRNA and protein expression, as well as inhibited the relative vitality of cells and the ability to form clones. After promoting CDH13 expression in K562-IMR cells, it inhabited the NF-κB signaling pathway and induced apoptosis in imatinib-resistant CML cells. LNP-saRNA (C3) was also observed to limit the growth of K562-IMR cells in vivo. From the above, the activation of CDH13 expression by saRNA promotes cell apoptosis by inhibiting the NF-κB signaling pathway to overcome to BCR-ABL1-independent resistance to imatinib in patients with CML.© 2024. The Author(s).