Related Experiment Video
Updated: May 23, 2025
08:44
A High-Throughput In Situ Method for Estimation of Hepatocyte Nuclear Ploidy in Mice
Published on: April 19, 2020
9.8K
GPATCH4 functions as a regulator of nucleolar R-loops in hepatocellular carcinoma cells
Yi-Ming Zhao1, Yan Jiang1, Jin-Zhu Wang1
1Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Nucleic Acids Research
|May 22, 2025
Summary
GPATCH4, an RNA-binding protein, drives hepatocellular carcinoma (HCC) by boosting protein synthesis and cell growth. Targeting GPATCH4 may offer new therapeutic strategies for liver cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Dysregulated RNA-binding proteins (RBPs) are linked to various cancers.
- The specific roles of RBPs in hepatocellular carcinoma (HCC) tumorigenesis are not fully understood.
Purpose of the Study:
- To identify and characterize novel RNA-binding proteins involved in HCC development.
- To elucidate the functional mechanism of GPATCH4 in HCC progression.
Main Methods:
- Multi-omics data integration to identify candidate RBPs in HCC.
- iCLIP-seq to map GPATCH4 in vivo RNA binding sites.
- In vitro and in vivo assays to assess the functional impact of GPATCH4 on HCC cells.
Main Results:
- GPATCH4 gene amplification (>70%) and high expression correlate with poor prognosis in HCC patients.
- GPATCH4 binds to ribosomal RNA (rRNA) and promotes HCC cell proliferation and transformation.
- GPATCH4 interacts with DDX21 in the nucleolus, unwinding rDNA R-loops to enhance rRNA transcription and protein synthesis.
Conclusions:
- GPATCH4 acts as an oncogenic RBP in HCC.
- GPATCH4 regulates nucleolar R-loops to control rRNA transcription via DDX21 interaction, promoting HCC.
- GPATCH4 represents a potential therapeutic target for HCC.
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