Landscape analysis of lncRNAs shows that DDX11-AS1 promotes cell-cycle progression in liver cancer through the PARP1/p53 axis

Cancer Lett. 2021 Nov 1:520:282-294. doi: 10.1016/j.canlet.2021.08.001. Epub 2021 Aug 8.

Abstract

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.

Keywords: DDX11-AS1; Hepatocellular carcinoma; Liver cancer; PARP1; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics
  • DNA Helicases / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mice
  • Poly (ADP-Ribose) Polymerase-1 / genetics*
  • RNA, Long Noncoding / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • DNA Helicases
  • DDX11 protein, human
  • DEAD-box RNA Helicases