Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China.
Environ Toxicol. 2021 Sep;36(9):1793-1801. doi: 10.1002/tox.23300. Epub 2021 Jun 4.
Long non-coding RNA (LncRNA) DUXAP9 expression was recently found to be higher in hepatocellular carcinoma (HCC) tissues and cells, and correlated with a shorter overall survival of HCC patients. However, its roles in HCC progression have never been revealed. Here, the roles of DUXAP9 in HCC cell stemness are explored as cancer stem cells (CSCs) contribute to one of the root of cancer progression. We found that DUXAP9 positively regulated HCC cell stemness, as characterized by the change of sphere-formation ability, ALDH activity and stemness marker expression. Further luciferase reporter, mRNA stability and RNA-RNA in vitro interaction assays indicated that DUXAP9 directly bound to the 3' untranslated region (UTR) of sox9, enhanced the mRNA stability of sox9 and thus increased sox9 expression. Notably, the effects induced by DUXAP9 on HCC cell stemness depended on sox9 expression. Therefore, this work identifies a novel DUXAP9/sox9 axis essential for HCC cell stemness.
长非编码 RNA (LncRNA) DUXAP9 的表达最近在肝癌 (HCC) 组织和细胞中被发现更高，并且与 HCC 患者的总生存率更短相关。然而，其在 HCC 进展中的作用从未被揭示。在这里，我们探索了 DUXAP9 在 HCC 细胞干性中的作用，因为癌症干细胞 (CSCs) 是癌症进展的根源之一。我们发现 DUXAP9 正向调节 HCC 细胞干性，其特征在于球体形成能力、ALDH 活性和干性标志物表达的变化。进一步的荧光素酶报告基因、mRNA 稳定性和体外 RNA-RNA 相互作用试验表明，DUXAP9 直接结合到 SOX9 的 3'非翻译区 (UTR)，增强了 SOX9 的 mRNA 稳定性，从而增加了 SOX9 的表达。值得注意的是，DUXAP9 对 HCC 细胞干性的影响取决于 SOX9 的表达。因此，这项工作确定了一个新的 DUXAP9/sox9 轴，对 HCC 细胞干性至关重要。
