BACKGROUND Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells. METHODS The study used both PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. The expression of miR-5195-3p was determined using quantitative real-time PCR. Cell viability, cell cycle distribution and apoptosis were analyzed using CCK-8 and flow cytometry assays. The target genes of miR-5195-3p were predicted with bioinformatics analysis and confirmed using the luciferase reporter assay. RESULTS MiR-5195-3p expression was lower in PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. Upregulation of miR-5195-3p enhanced the sensitivity of PTX-resistant TNBC cells to PTX treatment. EIF4A2 was confirmed as a potential target of miR-5195-3p. EIF4A2 knockdown imitated the effects of miR-5195-3p on chemosensitivity, while restoration of EIF4A2 rescued them. CONCLUSION These data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.

中文翻译：

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MicroRNA-5195-3p 通过下调 EIF4A2 增强三阴性乳腺癌对紫杉醇的化学敏感性。

背景基于紫杉醇 (PTX) 的化学疗法是包括三阴性乳腺癌 (TNBC) 在内的一系列癌症的标准治疗方法，但耐药性的增加已降低/已对其临床应用产生负面影响。先前的一项研究表明，miR-5195-3p 可以抑制肺癌细胞的生长。本研究旨在调查 miR-5195-3p 是否通过调节 TNBC 细胞中的靶基因来减弱对 PTX 的化学抗性。方法 该研究使用了 PTX 抗性肿瘤组织和 PTX 抗性 TNBC 细胞系。使用定量实时 PCR 测定 miR-5195-3p 的表达。使用 CCK-8 和流式细胞术分析细胞活力、细胞周期分布和细胞凋亡。通过生物信息学分析预测 miR-5195-3p 的靶基因，并使用荧光素酶报告基因测定进行确认。结果 MiR-5195-3p 在 PTX 抗性肿瘤组织和 PTX 抗性 TNBC 细胞系中的表达较低。miR-5195-3p 的上调增强了 PTX 抗性 TNBC 细胞对 PTX 治疗的敏感性。EIF4A2 被确认为 miR-5195-3p 的潜在靶标。EIF4A2 敲低模仿了 miR-5195-3p 对化学敏感性的影响，而 EIF4A2 的恢复则挽救了它们。结论 这些数据表明，miR-5195-3p 可能是通过靶向 EIF4A2 来逆转 TNBC 化疗耐药的潜在治疗靶点。miR-5195-3p 的上调增强了 PTX 抗性 TNBC 细胞对 PTX 治疗的敏感性。EIF4A2 被确认为 miR-5195-3p 的潜在靶标。EIF4A2 敲低模仿了 miR-5195-3p 对化学敏感性的影响，而 EIF4A2 的恢复则挽救了它们。结论 这些数据表明，miR-5195-3p 可能是通过靶向 EIF4A2 来逆转 TNBC 化疗耐药的潜在治疗靶点。miR-5195-3p 的上调增强了 PTX 抗性 TNBC 细胞对 PTX 治疗的敏感性。EIF4A2 被确认为 miR-5195-3p 的潜在靶标。EIF4A2 敲低模仿了 miR-5195-3p 对化学敏感性的影响，而 EIF4A2 的恢复则挽救了它们。结论 这些数据表明，miR-5195-3p 可能是通过靶向 EIF4A2 来逆转 TNBC 化疗耐药的潜在治疗靶点。