Department of Breast Surgery, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041 Sichuan Province China.
Cell Mol Biol Lett. 2019 Jul 1;24:47. doi: 10.1186/s11658-019-0168-7. eCollection 2019.
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.
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.
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.
These data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.
基于紫杉醇（PTX）的化疗是多种癌症的标准治疗方法，包括三阴性乳腺癌（TNBC），但耐药性的不断发展降低了其临床应用。先前的研究表明 miR-5195-3p 可以抑制肺癌细胞的生长。本研究旨在探讨 miR-5195-3p 是否通过调节 TNBC 细胞中的靶基因来减轻 PTX 的化疗耐药性。
该研究使用了 PTX 耐药的肿瘤组织和 PTX 耐药的 TNBC 细胞系。采用实时定量 PCR 检测 miR-5195-3p 的表达。采用 CCK-8 和流式细胞术检测细胞活力、细胞周期分布和细胞凋亡。采用生物信息学分析预测 miR-5195-3p 的靶基因，并通过荧光素酶报告基因实验进行验证。
miR-5195-3p 在 PTX 耐药的肿瘤组织和 PTX 耐药的 TNBC 细胞系中的表达较低。上调 miR-5195-3p 增强了 PTX 耐药的 TNBC 细胞对 PTX 治疗的敏感性。EIF4A2 被确认为 miR-5195-3p 的潜在靶基因。EIF4A2 敲低模拟了 miR-5195-3p 对化疗敏感性的影响，而 EIF4A2 的恢复则挽救了这种影响。
这些数据表明，miR-5195-3p 可能通过靶向 EIF4A2 成为逆转 TNBC 化疗耐药性的潜在治疗靶点。
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