LncRNA XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR-200c-3p to upregulate ANLN
LncRNA XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR-200c-3p to upregulate ANLN
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DOI：
10.1111/1440-1681.13307
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发表时间：
2020-05-06
影响因子：
2.9
通讯作者：
Zhou, Wei-Bing
中科院分区：
文献类型：
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作者：
Zhang, Min;Wang, Feng;Zhou, Wei-Bing
乳腺癌细胞对药物的耐药性是有效癌症化疗的主要障碍。本文旨在研究XIST在乳腺癌阿霉素耐药中的作用机制。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，发现MDA-MB-231/ADM细胞的阿霉素耐药性远高于MDA-MB-231细胞。MDA-MB-231/ADM细胞中XIST和ANLN的基因或蛋白表达也高于MDA-MB-231细胞。此外，XIST过表达通过促进ANLN表达促进细胞增殖并抑制阿霉素处理的MDA-MB-231细胞的凋亡。XIST沉默通过抑制ANLN表达抑制MDA-MB-231/ADM细胞增殖并促进凋亡。荧光素酶报告基因分析表明，XIST作为一种竞争性的内源性RNA抑制miR-200 c-3 p的表达，而miR-200 c-3 p又控制着其下游靶点ANLN。总之，这些数据表明，XIST通过海绵状miR-200 c-3 p上调ANLN来促进乳腺癌细胞对阿霉素的化学抗性。这项工作探讨了乳腺癌细胞中lncRNA XIST与阿霉素耐药性之间的关系，并强调了乳腺癌治疗的新治疗靶点。
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.