The GGH/HuR Complex Binds and Stabilizes mRNAs to Maintain Tumor Cell Cycle and DNA Replication.

ABSTRACT: GGH (Gamma-glutamyl hydrolase) is a folate metabolism enzyme that hydrolyzes intracellular polyglutamylated folates and is highly expressed in various cancers. It remains unclear whether GGH functions as an oncogene and its underlying mechanisms in tumor progression. Here, it is reported that GGH silencing inhibited the growth of lung cancer cells in vivo and in vitro. The oncogenic function of GGH relied on its non-canonical role as a novel RNA-binding protein, which maintained the cell cycle and DNA replication by stabilizing target mRNAs. Furthermore, GGH bound to the GC-rich motif in the 5' untranslated region of mRNAs, such as CDC6 and CCND1. Additionally, GGH directly interacts with HuR (Human Antigen R), a well-characterized RNA-binding protein critical for mRNA stability in cancer.

SUBMITTER: Li Y 

PROVIDER: S-EPMC12622440 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature