Although long non-coding RNAs (lncRNAs) play important roles in tumorigenesis, the underlying mechanisms are unclear. Transcriptomic analysis of 33 hepatocellular carcinoma (HCC) samples revealed that the most enriched pathway for differentially expressed genes was related to the cell cycle process, where DDX11-AS1 is the most significant lncRNA. Upregulation of DDX11-AS1 expression through demethylation was significantly associated with a poor prognosis. Further mechanistic studies revealed that DDX11-AS1 promoted the growth of HCC by interacting with PARP1 through attenuating its binding to p53, leading to downregulated expression of p53 for inhibiting the transcription of downstream genes such as p21. Knockdown of DDX11-AS1 expression in xenograft mice using anti-DDX11-AS1 oligonucleotide suppressed liver tumor proliferation. These findings indicate that DDX11-AS1 plays a role in the development of liver cancer by affecting the cell cycle.

尽管长链非编码 RNA (lncRNA) 在肿瘤发生中起重要作用，但其潜在机制尚不清楚。对 33 个肝细胞癌 (HCC) 样本的转录组学分析显示，差异表达基因最丰富的途径与细胞周期过程有关，其中DDX11-AS1是最重要的 lncRNA。通过去甲基化上调DDX11-AS1表达与预后不良显着相关。进一步的机制研究表明，DDX11-AS1通过与 PARP1 相互作用，通过减弱其与p53 的结合来促进 HCC 的生长，导致p53 的表达下调，从而抑制下游基因的转录，例如第 21 页。使用抗DDX11-AS1寡核苷酸在异种移植小鼠中敲低 DDX11-AS1表达可抑制肝肿瘤增殖。这些发现表明DDX11-AS1通过影响细胞周期在肝癌的发展中发挥作用。