RBM12 Maintains Glioma Stem Cells by Activating Amino Acid-Dependent mTORC1 Signaling via SLC7A5 mRNA Stabilization
Hong Lei1, Wenlong Luo1, Shu Zhou1
1College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 22, 2026
Summary
The RNA-binding protein RBM12 promotes glioblastoma growth by increasing amino acid uptake via SLC7A5, activating the mTORC1 pathway. Inhibiting this RBM12-SLC7A5 axis offers a potential therapeutic strategy for glioblastoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer stem cells, including glioma stem cells (GSCs), exhibit altered amino acid metabolism crucial for proliferation.
- The precise molecular mechanisms driving metabolic reprogramming in GSCs are not fully understood.
Purpose of the Study:
- To elucidate the role of the RNA-binding protein RBM12 in GSC proliferation and glioblastoma (GBM) growth.
- To identify the molecular targets and pathways regulated by RBM12 in GBM.
Main Methods:
- Investigated the function of RBM12 in GSCs and GBM models.
- Analyzed the impact of RBM12 on amino acid transporter SLC7A5 mRNA stability.
- Examined the role of ALKBH5 in mediating RBM12's effect on SLC7A5 mRNA.
- Assessed the therapeutic efficacy of targeting the RBM12-SLC7A5 axis using JPH203.
Main Results:
- RBM12 increases intracellular large neutral amino acids by stabilizing SLC7A5 mRNA.
- RBM12 recruits ALKBH5 to demethylate m6A modifications on SLC7A5 mRNA, enhancing its stability.
- Activation of the mTORC1 pathway by elevated amino acids promotes GSC proliferation, self-renewal, and GBM growth.
- Pharmacological inhibition of the RBM12-SLC7A5 axis with JPH203 suppressed GBM growth.
Conclusions:
- RBM12 plays a critical role in GBM pathogenesis by regulating amino acid metabolism and mTORC1 signaling.
- The RBM12-SLC7A5-mTORC1 axis represents a novel vulnerability in GBM.
- Targeting the RBM12-SLC7A5 pathway holds therapeutic promise for glioblastoma treatment.
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