Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Clin Exp Pharmacol Physiol. 2020 Aug;47(8):1464-1472. doi: 10.1111/1440-1681.13307. Epub 2020 May 6.
The resistance of breast cancer cells to drugs is a major obstacle to effective cancer chemotherapy. Here, we study the function mechanisms of long non-coding RNA XIST in chemoresistance of breast cancer to doxorubicin. We examined the 50% inhibitive concentration of doxorubicin to MDA-MB-231 and MDA-MB-231/ADM cells, showing that the doxorubicin resistance of MDA-MB-231/ADM cells was much higher than MDA-MB-231 cells. The gene or protein expression of XIST and ANLN were also higher in MDA-MB-231/ADM cells than that in MDA-MB-231 cells. Moreover, XIST overexpression promoted cell proliferation and inhibited apoptosis of doxorubicin-treated MDA-MB-231 cells by promoting ANLN expression. XIST silencing inhibited cell proliferation and promoted apoptosis of doxorubicin-treated MDA-MB-231/ADM cells by inhibiting ANLN expression. Luciferase reporter assay showed that XIST functioned as a competing endogenous RNA to repress miR-200c-3p, which controlled its downstream target ANLN. In conclusion, these data reveal that XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR-200c-3p to upregulate ANLN. This work explores the relationship between lncRNA XIST and doxorubicin resistance in breast cancer cells and highlights a novel therapeutic target for the treatment of breast cancer.
乳腺癌细胞对药物的耐药性是癌症化疗有效治疗的主要障碍。在这里，我们研究了长非编码 RNA XIST 在乳腺癌细胞对阿霉素耐药中的功能机制。我们检测了阿霉素对 MDA-MB-231 和 MDA-MB-231/ADM 细胞的 50%抑制浓度，结果表明 MDA-MB-231/ADM 细胞对阿霉素的耐药性明显高于 MDA-MB-231 细胞。XIST 和 ANLN 的基因或蛋白表达在 MDA-MB-231/ADM 细胞中也高于 MDA-MB-231 细胞。此外，XIST 过表达通过促进 ANLN 的表达促进了阿霉素处理的 MDA-MB-231 细胞的增殖和抑制了细胞凋亡。XIST 沉默通过抑制 ANLN 的表达抑制了阿霉素处理的 MDA-MB-231/ADM 细胞的增殖并促进了细胞凋亡。荧光素酶报告实验表明，XIST 作为竞争性内源性 RNA 发挥作用，抑制了 miR-200c-3p，从而控制其下游靶标 ANLN。总之，这些数据表明，XIST 通过海绵吸附 miR-200c-3p 来上调 ANLN，从而促进乳腺癌细胞对阿霉素的耐药性。这项工作探讨了长链非编码 RNA XIST 与乳腺癌细胞中阿霉素耐药之间的关系，并强调了治疗乳腺癌的新的治疗靶点。
