4.7 Article

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

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CANCER LETTERS
卷 520, 期 -, 页码 282-294

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.08.001

关键词

lncRNA; DDX11-AS1; Hepatocellular carcinoma; Liver cancer; PARP1

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资金

  1. China Precision Medicine Initiative [2016YFC0906300]
  2. Major Program of National Natural Sci-ence Foundation of China [81790634]
  3. Research Center for Air Pollution and Health of Zhejiang University
  4. Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

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DDX11-AS1 upregulation through demethylation is associated with poor prognosis in hepatocellular carcinoma. Mechanistically, DDX11-AS1 interacts with PARP1 to attenuate its binding to p53, resulting in downregulated p53 expression and inhibition of downstream gene transcription, ultimately promoting liver cancer growth.
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.

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