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.

中文翻译：

---

长链非编码RNA DUXAP9通过直接与sox9相互作用促进肝癌细胞干细胞

最近发现长链非编码 RNA (LncRNA) DUXAP9 在肝细胞癌 (HCC) 组织和细胞中的表达较高，并且与 HCC 患者的总生存期较短相关。然而，它在 HCC 进展中的作用从未被揭示。在这里，探索了 DUXAP9 在 HCC 细胞干性中的作用，因为癌症干细胞 (CSC) 有助于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 RNA-RNA 体外相互作用测定表明，DUXAP9 直接与 sox9 的 3' 非翻译区 (UTR) 结合，增强了 sox9 的 mRNA 稳定性，从而增加了 sox9 的表达。尤其，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对 HCC 细胞干性至关重要的新型 DUXAP9/sox9 轴。