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LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells

Authors: Xiong, Minmin; Wu, Mengshi; Dan Peng; Huang, Weijun; Chen, Zehong; Ke, Haoxian; Chen, Zewen; Song, Wu; Zhao, Yonghua; Xiang, Andy P.; Zhong, Xiaomin

Online: https://www.nature.com/articles/s41419-020-03318-8

Issue: Cell Death Dis. 2021 Jan 6;12(1):24.


Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis. MALAT1 could efficiently mediate the suppressive function of DANCR on apoptosis. Mechanistic studies found the RNA-binding protein QK served as an interacting partner of both DANCR and MALAT1, and the protein level of QK was subjected to the regulation by DANCR. Furthermore, QK was able to modulate the RNA stability of MALAT1, and the interaction between QK and MALAT1 was controlled by DANCR. In addition, QK could mediate the function of DANCR in regulating the expression of MALAT1 and suppressing apoptosis. These results revealed DANCR played a critical role in Doxorubicin-induced apoptosis in colorectal cancer cells, which was achieved by the interaction between DANCR and QK to enhance the expression of MALAT1.