LncRNA XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR‐200c‐3p to upregulate ANLN

• Published in: Clinical and experimental pharmacology & physiology 2020-08, Vol.47 (8), p.1464-1472
• Main Authors: Zhang, Min, Wang, Feng, Xiang, Zhen, Huang, Teng, Zhou, Wei‐Bing
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chemoresistance; Chemotherapy; competing endogenous RNA; Doxorubicin; Doxorubicin - pharmacology; doxorubicin resistance; Drug development; Drug Resistance, Neoplasm - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; Non-coding RNA; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Therapeutic applications; Up-Regulation - drug effects; XIST/miR‐200c‐3p/ANLN
• ISSN: 0305-1870; 1440-1681; 1440-1681
• DOI: 10.1111/1440-1681.13307

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.