MicroRNA (miR)‑125a‑5p represses tafazzin phospholipid‑lysophospholipid transacylases (TAFAZZIN) expression and inhibits the epithelial‑mesenchymal transition (EMT) of ovarian cancer cells. EMT was found to have a crucial role in the acquisition of chemoresistance. Thus, the present study aimed to determine whether miR‑125a‑5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer. The expression of miR‑125a‑5p/TAFAZZIN and its association with chemotherapy response were determined in tissue samples from patients with breast cancer. Furthermore, the effects of miR‑125a‑5p on breast cancer cells were elucidated using cell proliferation and cell apoptosis assays. Then, the regulatory mechanism of miR‑125a‑5p in breast cancer was investigated by reverse transcription‑quantitative PCR, western blotting, dual‑luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that miR‑125a‑5p inhibited the EMT of MCF‑7/adriamycin (Adr) breast cancer cells, as well as decreased the proliferation and increased the apoptosis of breast cancer cells treated with Adr/docetaxel. In addition, miR‑125a‑5p downregulated the expression levels of TAFAZZIN, Transglutaminase 2, phosphorylated‑AKT, N‑cadherin, vimentin and proliferating cell nuclear antigen, and significantly increased those of E‑cadherin, cleaved caspase-3 and Bax in MCF7/Adr cells. Similar results were obtained with small interfering RNA‑TAFAZZIN. Moreover, TAFAZZIN was identified as a direct target of miR‑125a‑5p in MCF7/Adr breast cancer cells. In addition, increased miR‑125a‑5p expression was observed in breast tumors from patients exhibiting a chemotherapy response, and TAFAZZIN mRNA expression was elevated in patients with no chemotherapy response. Hence, miR‑125a‑5p expression was negatively correlated with TAFAZZIN mRNA expression in breast cancer tissues. All these data suggested that miR‑125a‑5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer and, therefore, has potential as a novel therapeutic target for this disease.

中文翻译：

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miR‑125a‑5p 通过负调节乳腺癌中的 TAFAZZIN 信号传导逆转上皮间质转化并恢复药物敏感性。

MicroRNA (miR)-125a-5p 抑制 tafazzin 磷脂-溶血磷脂转酰基酶 (TAFAZZIN) 表达并抑制卵巢癌细胞的上皮间质转化 (EMT)。发现 EMT 在获得化学抗性中起关键作用。因此，本研究旨在确定 miR-125a-5p 是否通过负调节乳腺癌中的 TAFAZZIN 逆转 EMT 并恢复药物敏感性。在乳腺癌患者的组织样本中确定了 miR-125a-5p/TAFAZZIN 的表达及其与化疗反应的关联。此外，使用细胞增殖和细胞凋亡测定阐明了 miR-125a-5p 对乳腺癌细胞的影响。然后，通过逆转录定量PCR、蛋白质印迹、双荧光素酶报告基因和 RNA 免疫沉淀测定。结果表明，miR-125a-5p 抑制 MCF-7/阿霉素 (Adr) 乳腺癌细胞的 EMT，并减少用 Adr/多西他赛处理的乳腺癌细胞的增殖和增加细胞凋亡。此外，miR-125a-5p 下调 TAFAZZIN、转谷氨酰胺酶 2、磷酸化 AKT、N-钙粘蛋白、波形蛋白和增殖细胞核抗原的表达水平，并显着增加 MCF7 中 E-钙粘蛋白、切割的 caspase-3 和 Bax 的表达水平/Adr 细胞。使用小干扰 RNA-TAFAZZIN 也获得了类似的结果。此外，TAFAZZIN 被确定为 MCF7/Adr 乳腺癌细胞中 miR-125a-5p 的直接靶标。此外，在表现出化疗反应的患者的乳腺肿瘤中观察到 miR-125a-5p 表达增加，无化疗反应的患者中 TAFAZZIN mRNA 表达升高。因此，miR-125a-5p的表达与乳腺癌组织中TAFAZZIN mRNA的表达呈负相关。所有这些数据表明，miR-125a-5p 通过对乳腺癌中的 TAFAZZIN 负调控来逆转 EMT 并恢复药物敏感性，因此有可能成为该疾病的新治疗靶点。