The GGH/HuR Complex Binds and Stabilizes mRNAs to Maintain Tumor Cell Cycle and DNA Replication
Yu Li1,2, Xinrui Li2, Yuhui Du2,3
1Department of Critical Care Medicine, Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 20, 2025
Summary
Gamma-glutamyl hydrolase (GGH) acts as an oncogene in lung cancer by stabilizing key mRNAs, promoting cell growth. Silencing GGH inhibited tumor progression, highlighting it as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Gamma-glutamyl hydrolase (GGH) is a folate metabolism enzyme highly expressed in cancers.
- Its role as an oncogene and underlying mechanisms in tumor progression are not fully understood.
Purpose of the Study:
- To investigate the oncogenic function of GGH in lung cancer.
- To elucidate the molecular mechanisms by which GGH promotes tumor progression.
Main Methods:
- GGH gene silencing in lung cancer cells (in vitro and in vivo).
- RNA-binding assays to identify mRNA targets and binding motifs.
- Co-immunoprecipitation to study protein-RNA interactions (GGH, HuR).
- Analysis of GGH expression in lung cancer tissues and correlation with patient survival.
Main Results:
- GGH silencing significantly inhibited lung cancer cell growth.
- GGH functions as an RNA-binding protein, stabilizing target mRNAs like CDC6 and CCND1.
- GGH interacts with HuR, forming a ternary complex that may enhance mRNA stability.
- High GGH expression in lung cancer tissues correlates with poorer patient survival.
Conclusions:
- GGH possesses oncogenic functions in lung cancer through a non-canonical RNA-binding role.
- GGH stabilizes cell cycle and DNA replication-related mRNAs.
- GGH represents a potential therapeutic target for lung cancer treatment.
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