Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Center for Stem Cell Biology and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, 510080, Guangzhou, China.
Center of Gastrointestinal Surgery, Center of Gastric Cancer, The First Affiliated Hospital, Sun Yat-Sen University, 510080, Guangzhou, China.
Cell Death Dis. 2021 Jan 6;12(1):24. doi: 10.1038/s41419-020-03318-8.
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.
长链非编码 RNA（lncRNA）DANCR 已被报道参与干细胞分化和肿瘤发生等关键过程。在高内涵筛选涉及多柔比星诱导细胞凋亡的 lncRNA 时，我们发现 DANCR 受多柔比星抑制，并且作为结直肠癌中细胞凋亡的重要抑制剂。进一步的研究表明，DANCR 通过增强 MALAT1 的 RNA 稳定性来促进致癌 lncRNA MALAT1 的表达，从而抑制细胞凋亡。MALAT1 可以有效地介导 DANCR 对细胞凋亡的抑制功能。机制研究发现 RNA 结合蛋白 QK 是 DANCR 和 MALAT1 的相互作用伙伴，并且 QK 的蛋白水平受到 DANCR 的调节。此外，QK 可以调节 MALAT1 的 RNA 稳定性，并且 QK 和 MALAT1 之间的相互作用受 DANCR 控制。此外，QK 可以介导 DANCR 在调节 MALAT1 表达和抑制细胞凋亡中的功能。这些结果揭示了 DANCR 通过与 QK 的相互作用在结直肠癌细胞中多柔比星诱导的细胞凋亡中发挥关键作用，从而增强 MALAT1 的表达。
