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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular
Yong Li1, Wenlong Zhuang2, Maosheng Huang2
1Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 201129, China; Department of Hepatobiliary Surgery, Suqian First Hospital, Suqian, Jiangsu, 223800, China.
Abstract:
Long noncoding RNAs (lncRNAs), a group of transcripts without protein coding potential, have been reported to play critical roles in progression of hepatocellular carcinoma (HCC). However, the biological role of DDX11-AS1 in HCC is not clear. In this study, we found that DDX11-AS1 expression was dramatically higher in HCC tissues and cell lines. Higher DDX11-AS1 expression predicted poor overall survival of patients. Functionally, the proliferation, cell cycle progression, migration, and invasion of HCC cells were inhibited by DDX11-AS1 silencing, while promoted by ectopic expression of DDX11-AS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays validated that DDX11-AS1 suppressed LATS2 expression by interacting with EZH2 and DNMT1 in HCC cells. Knockdown of DDX11-AS1 increased the mRNA and protein levels of LATS2. Overexpression of LATS2 abolished the promotive effect of DDX11-AS1 on cell growth and invasion. Besides, DDX11-AS1 promoted tumor formation in vivo. The mRNA levels of LATS2 were markedly decreased in tumor tissues and negatively correlated with DDX11-AS1 expression. Taken together, our data indicated that DDX11-AS1 may be a novel oncogene in hepatocarcinogenesis by repressing LATS2, providing a potential therapeutic target for HCC treatment.
Insights
Long noncoding RNA DDX11-AS1 is highly expressed in hepatocellular carcinoma (HCC), promoting tumor growth and invasion by suppressing LATS2. This suggests DDX11-AS1 is a potential oncogene and therapeutic target for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in hepatocellular carcinoma (HCC) progression.
- The specific role of DDX11-AS1 in HCC pathogenesis remains largely unknown.
Purpose of the Study:
- To investigate the biological function and clinical significance of DDX11-AS1 in hepatocellular carcinoma.
- To elucidate the molecular mechanism underlying DDX11-AS1's role in HCC.
Main Methods:
- Quantitative real-time PCR and western blotting to assess gene expression.
- Cell proliferation, migration, invasion, and cell cycle assays.
- RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.
- In vivo tumor formation assays.
Main Results:
- DDX11-AS1 expression is significantly upregulated in HCC tissues and cell lines, correlating with poor patient survival.
- DDX11-AS1 silencing inhibits HCC cell proliferation, migration, and invasion, while its overexpression promotes these processes.
- DDX11-AS1 interacts with EZH2 and DNMT1 to suppress LATS2 expression, thereby promoting HCC growth and invasion.
- DDX11-AS1 promotes tumor formation in vivo, and LATS2 expression is negatively correlated with DDX11-AS1 levels in tumor tissues.
Conclusions:
- DDX11-AS1 acts as a novel oncogene in hepatocarcinogenesis by repressing LATS2.
- DDX11-AS1 represents a potential therapeutic target for hepatocellular carcinoma treatment.
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