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journal article·2026-06-22Open access

RBM12 Maintains Glioma Stem Cells by Activating Amino Acid‐Dependent mTORC1 Signaling via SLC7A5 mRNA Stabilization

Hong Lei, Wenlong Luo, Shu Zhou, Lihao Wan, Peng Ling, Zhihua Huang, Zhihua Qian, Chenfei Lu, Mengyue Guo, Zhen Xue, Jun Qin, Ningwei Zhao, Jianghong Man, Wenchao Zhou, Zhiqiang Dong, Shutong Xu, Zhipeng Zhou, Xiuxing Wang, Weiwei Tao

Advanced Science
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Abstract

ABSTRACT Reprogramming of amino acid metabolism is crucial for the rapid proliferation of cancer cells, including cancer stem cells. However, the molecular mechanisms underlying this reprogramming in glioma stem cells (GSCs) remain poorly understood. Here, we report that the RNA‐binding protein RBM12 increases the intracellular levels of large neutral amino acids, thereby activating the mTORC1 pathway and promoting GSC proliferation, self‐renewal, and glioblastoma (GBM) growth. Mechanistically, RBM12 stabilizes the mRNA of the amino acid transporter SLC7A5 , thereby increasing intracellular levels of large neutral amino acids, which subsequently activates the mTORC1 pathway. Further studies reveal that RBM12 enhances SLC7A5 mRNA stability by recruiting ALKBH5 to remove m 6 A modifications on SLC7A5 mRNA. Importantly, pharmacological inhibition of the RBM12‐SLC7A5 axis using the SLC7A5 inhibitor JPH203 effectively suppresses GBM growth. These findings elucidate a novel role for RBM12‐SLC7A5 signaling in the malignant growth of GBM and highlight the therapeutic potential of targeting this axis for GBM treatment.
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Research context

OpenAlex topics: RNA modifications and cancer · Amino Acid Enzymes and Metabolism · Cancer, Hypoxia, and Metabolism

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

College of Biomedicine and Health College of Life Science and Technology Huazhong Agricultural University Wuhan Hubei China

National Health Commission Key Laboratory of Antibody Techniques Department of Cell Biology School of Basic Medical Sciences Nanjing Medical University Nanjing Jiangsu China

Department of Neurosurgery The First Affiliated Hospital of Nanjing Medical University Nanjing Medical University Nanjing Jiangsu China

Hubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction Taihe Hospital Hubei University of Medicine Shiyan Hubei China

Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China

China Exposomics Institute Shanghai China

National Center of Biomedical Analysis Beijing China

Department of Pathology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China

Funding

National Natural Science Foundation of China · Fundamental Research Funds for the Central Universities · Natural Science Foundation of Hubei Province

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