Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.

中文翻译：

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多西他赛耐药三阴性乳腺癌细胞衍生的外泌体 lncRNA LINC00667 通过靶向 miR-200b-3p/Bcl-2 轴降低乳腺癌细胞对多西他赛的化学敏感性。

多西他赛 (TXT) 耐药性的发展是三阴性乳腺癌 (TNBC) 治疗的主要障碍。此外，化学抗性细胞衍生的外泌体能够通过运输 lncRNA 改变化学敏感性受体细胞的化学反应。已经表明，lncRNA LINC00667 水平在乳腺癌组织中显着升高。因此，我们探讨了 TXT 抗性 TNBC 细胞衍生的外泌体中 LINC00667 水平是否增加。此外，还研究了源自 TXT 抗性 TNBC 细胞的外泌体 LINC00667 是否会影响 TXT 敏感 TNBC 细胞中的 TXT 敏感性。在本研究中，外泌体是从 TXT 抗性 TNBC 细胞和 TXT 敏感 TNBC 细胞中分离出来的。接下来，用 RT-qPCR 检测分离的外泌体中 LINC00667 的水平。我们发现，与 TXT 敏感的 TNBC 细胞衍生的外泌体相比，TXT 抗性 TNBC 细胞衍生的外泌体中 LINC00667 的表达明显升高。此外，LINC00667 可以通过外泌体从 TXT 抗性 TNBC 细胞转移到 TNBC 细胞。此外，TXT 抗性 TNBC 细胞分泌的外泌体 LINC00667 通过上调 Bcl-2 显着降低了 TNBC 细胞对 TXT 的敏感性。同时，LINC00667的下调通过Bcl-2的下调显着增强了TXT抗性TNBC细胞对TXT的敏感性。此外，LINC00667 被认为是海绵状 miR-200b-3p 的 ceRNA，从而提高 Bcl-2 表达。总的来说，TXT 耐药 TNBC 细胞衍生的外泌体 LINC00667 可通过调节 miR-200b-3p/Bcl-2 轴降低 TNBC 细胞对 TXT 的化学敏感性。