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LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells
Cell Death & Disease ( IF 9 ) Pub Date : 2021-01-06 , DOI: 10.1038/s41419-020-03318-8
Minmin Xiong 1 , Mengshi Wu 1 , Dan Peng 1 , Weijun Huang 1 , Zehong Chen 2 , Haoxian Ke 1 , Zewen Chen 3 , Wu Song 2 , Yonghua Zhao 4 , Andy P Xiang 1 , Xiaomin Zhong 1
Affiliation  

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.



中文翻译:

LncRNA DANCR通过稳定结直肠癌细胞中的MALAT1表达抑制多柔比星诱导的细胞凋亡

据报道,长链非编码 RNA (lncRNA) DANCR 参与干细胞分化和肿瘤发生等关键过程。在对参与多柔比星诱导的细胞凋亡的 lncRNA 的高通量筛选中,我们发现 DANCR 被多柔比星抑制,并且它在结直肠癌中充当重要的细胞凋亡抑制因子。进一步的研究表明,DANCR 通过增强 MALAT1 的 RNA 稳定性来抑制细胞凋亡,从而促进致癌 lncRNA MALAT1 的表达。MALAT1 可以有效介导 DANCR 对细胞凋亡的抑制作用。机理研究发现,RNA结合蛋白QK作为DANCR和MALAT1的相互作用伙伴,QK的蛋白水平受DANCR调控。此外,QK 能够调节 MALAT1 的 RNA 稳定性,QK 和 MALAT1 之间的相互作用受 DANCR 控制。此外,QK还可介导DANCR调节MALAT1表达和抑制细胞凋亡的功能。这些结果表明 DANCR 在阿霉素诱导的结直肠癌细胞凋亡中起关键作用,这是通过 DANCR 和 QK 之间的相互作用增强 MALAT1 的表达来实现的。

更新日期:2021-01-08
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