State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cancer Lett. 2021 Nov 1;520:282-294. doi: 10.1016/j.canlet.2021.08.001. Epub 2021 Aug 8.
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.
虽然长链非编码 RNA(lncRNA)在肿瘤发生中发挥重要作用,但潜在机制尚不清楚。对 33 个肝细胞癌(HCC)样本的转录组分析显示,差异表达基因最富集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 的表达与预后不良显著相关。进一步的机制研究表明,DDX11-AS1 通过与 PARP1 相互作用来促进 HCC 的生长,从而减弱其与 p53 的结合,导致 p53 的表达下调,从而抑制下游基因如 p21 的转录。使用抗 DDX11-AS1 寡核苷酸在异种移植小鼠中敲低 DDX11-AS1 的表达可抑制肝肿瘤的增殖。这些发现表明,DDX11-AS1 通过影响细胞周期在肝癌的发展中起作用。