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Overexpression of microRNA-24 increases the sensitivity to paclitaxel in drug-resistant breast carcinoma cell lines via targeting ABCB9

机译:通过靶向ABCB9microRNA-24的过表达提高了耐药性乳腺癌细胞株对紫杉醇的敏感性

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摘要

Paclitaxel has been widely used in the treatment of breast cancer. However, the development of drug resistance often increases the failure of chemotherapy. Growing evidence has reported the significant role of microRNAs (miRs) in drug resistance. The present study identified that miR-24 was significantly downregulated in paclitaxel-resistant (PR) breast cancer patients and in MCF-7/PR human breast carcinoma cells, and that overexpression of miR-24 could increase the effect of paclitaxel on drug-resistant breast carcinoma cells. Furthermore, miR-24 could directly bind to the 3′-untranslated region of ATP binding cassette B9 to downregulate its expression, thereby reducing drug transportation and improving the anti-tumor effect of paclitaxel on breast cancer cells. In vivo experiments also demonstrated that overexpression of miR-24 could increase the sensitivity of drug-resistant MCF-7 cells to paclitaxel. In conclusion, the present results suggested a novel function for miR-24 in reducing paclitaxel resistance in breast cancer, which may be of important clinical significance.
机译:紫杉醇已被广泛用于治疗乳腺癌。但是,耐药性的发展通常会增加化疗的失败率。越来越多的证据报道了microRNA(miR)在耐药中的重要作用。本研究发现,在耐紫杉醇(PR)的乳腺癌患者和MCF-7 / PR人乳腺癌细胞中,miR-24显着下调,miR-24的过表达可增强紫杉醇对耐药性的作用乳腺癌细胞。此外,miR-24可以直接与ATP结合盒B9的3'-非翻译区结合以下调其表达,从而减少药物转运并提高紫杉醇对乳腺癌细胞的抗肿瘤作用。体内实验还表明,miR-24的过表达可以增加耐药MCF-7细胞对紫杉醇的敏感性。总之,目前的结果提示miR-24在降低乳腺癌中对紫杉醇的耐药性方面具有新功能,这可能具有重要的临床意义。

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