癌症干细胞样细胞 (CSLC) 驱动肿瘤进展和化疗耐药。 EXO1 和 TLS 聚合酶的共同努力可保护 DNA 完整性，免受化疗药物的影响。由于缺乏潜在的药物靶点，非小细胞肺癌（NSCLC）患者的治疗选择很少。在当前情况下，microRNA 提供了根除 CSLC 的潜在途径。通过流式细胞术评估了 EXO1 下调对 CSLC 扩增的影响。 EXO1、Polη 和 Polι 的共定位通过免疫共沉淀和共焦成像进行了验证。使用流式细胞术和免疫组织化学在细胞系和异种移植物中评估 Polη 和 Polι 共同下调对 CSLC 存活、修复合成和诱变的影响。研究了靶向 EXO1 的 MicroRNA 在 CSLC 调节中的作用。NSCLC CSLC 中 EXO1 下调会诱导 DNA 损伤，引发细胞凋亡并增强顺铂敏感性。它与 Polη 和 Polι 共同修复 DNA，导致 CSLC 中的顺铂耐药。 Polη 和 Polι 的缺失会损害修复并减少顺铂诱导的突变。异种移植物中 Polη 和 Polι 的共同下调显着降低了肿瘤增殖。如机制研究所示，miR-3163 过表达通过靶向 EXO1/Polη/Polι 轴使 CSLC 对顺铂敏感。这项研究揭示了一条涉及 EXO1/Polη/Polι 轴和 miR-3163 的新调控途径，为 NSCLC 中 CSLC 的调控提供了见解。 EXO1/Polη/Polι 轴由 miR-3163 靶向，从而抑制 NSCLC CSLC 中的细胞生长并诱导细胞凋亡。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Cancer stem-like cells (CSLCs) drive tumour progression and chemoresistance. The concerted efforts of EXO1 and TLS polymerases safeguard DNA integrity against chemotherapeutic drugs. In absence of potential drug targets, non-small cell lung carcinoma (NSCLC) patients have few therapeutic options. In current scenario, microRNAs offer a potential avenue for eradicating CSLCs.EXO1 downregulation impact on CSLCs expansion was assessed via flow cytometry. Co-localisation of EXO1, Polη and Polι was validated through co-immunoprecipitation and confocal-imaging. The effects of co-downregulation of Polη and Polι on CSLC survival, repair synthesis, and mutagenesis were evaluated using flow cytometry and immunohistochemistry in cell lines and xenografts. MicroRNA targeting EXO1 was studied for its role in CSLCs regulation.EXO1 downregulation in NSCLC CSLCs induces DNA lesions, triggering apoptosis and enhances cisplatin sensitivity. It collaborates with Polη and Polι in DNA repair, contributing to cisplatin resistance in CSLCs. Absence of Polη and Polι impairs repair and reduces cisplatin-induced mutagenesis. Co-downregulation of Polη and Polι in xenografts reduces tumour proliferation significantly. MiR-3163 overexpression sensitises CSLCs to cisplatin via targeting EXO1/Polη/Polι axis, as shown in mechanistic studies.This study unveils a novel regulatory pathway involving EXO1/Polη/Polι axis and miR-3163, providing insights into CSLCs regulation in NSCLC. EXO1/Polη/Polι axis targeted by miR-3163, resulting in the inhibition of cell growth and induction of apoptosis in NSCLC CSLCs.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.