2. Academic Validation
  3. NAT10-mediated N4-acetylcytidine (ac4C) modification of PIK3R2 mRNA promotes malignant progression of glioblastoma

NAT10-mediated N4-acetylcytidine (ac4C) modification of PIK3R2 mRNA promotes malignant progression of glioblastoma

  • Cell Death Dis. 2025 Dec 17. doi: 10.1038/s41419-025-08328-y.
Xiannan Meng # 1,  Tao Dong # 1,  Jiayu Xu # 2,  Kaiwen Tian 3,  Wendong Yang 1,  Zixuan Liu 1,  Yongjing Qian 1,  Dingding Liu 1,  Changxiu Chen 4,  Jin Bai 5 6 7,  Hongmei Yong 8,  Xiaojin Wu 9 10,  Zhigang Shen 11 12
Affiliations

Affiliations

  • 1 Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China.
  • 3 Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Department of Pediatrics, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 5 Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 6 Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 7 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 8 Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China. [email protected].
  • 9 Cancer Center, Xuzhou Central Hospital, Southeast University, Xuzhou, Jiangsu, China. [email protected].
  • 10 Department of Radiation Oncology, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 11 Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 12 Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • # Contributed equally.
PMID: 41408025 DOI: 10.1038/s41419-025-08328-y
Abstract

Glioma is the most common primary tumor in the central nervous system, with glioblastoma (GBM) representing one of the most malignant forms, accounting for 46.1% of cases. GBM is characterized by rapid progression, high malignancy, and poor prognosis, with median survival remaining less than 15 months despite combined surgery, radiotherapy, and chemotherapy. NAT10, the only known acetyltransferase mediating N4-acetylcytidine (ac4C) modification in eukaryotes, has been implicated in promoting tumorigenesis and progression in colon Cancer, bladder Cancer, pancreatic ductal Cancer, among Others. In this study, we found that NAT10 is highly expressed in GBM and is positively correlated with malignant pathological features and poor prognosis in patients. In vitro experiments demonstrated that NAT10 promotes tumor proliferation, migration, and invasion. In vivo experiments further confirmed that NAT10 facilitates malignant progression of tumors. Mechanistically, we revealed that NAT10 regulates PIK3R2 stabilization through ac4C modification, thereby participating malignant characterization of GBM. Additionally, our data demonstrated a positive correlation between NAT10 and PIK3R2 in glioma patients. Taken together, our findings strongly suggest that NAT10 is a potential therapeutic target for GBM.

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