2. Academic Validation
  3. Identification of Glutathione Synthetase as a Therapeutic Target for Cervical Cancer via Combining Bioinformatics and Experimental Validation

Identification of Glutathione Synthetase as a Therapeutic Target for Cervical Cancer via Combining Bioinformatics and Experimental Validation

  • J Cell Mol Med. 2025 Dec;29(24):e70968. doi: 10.1111/jcmm.70968.
Meini Pan 1 2 3,  Tingzhuang Yi 2 3,  Peng Lei 4,  Jiangmi Mo 5,  Jinyan Lan 5,  Yulu Ye 5,  Hongqian Wang 6,  Cheng Yuan 7 8 9,  Zhaohe Huang 1 10
Affiliations

Affiliations

  • 1 Guangxi Medical University, Nanning, China.
  • 2 Department of Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
  • 3 Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Baise, China.
  • 4 Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
  • 5 Youjiang Medical University for Nationalities, Baise, China.
  • 6 Department of Nasopharyngeal Oncology, Red Cross Hospital of Yulin City, Yulin, China.
  • 7 Department of Oncology, Yichang Central People's Hospital and The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
  • 8 Tumor Prevention and Treatment Center of Three Gorges University, Cancer Research Institute of Three Gorges University, Yichang, China.
  • 9 Clinical Medical Research Center for Precision Diagnosis and Treatment of Lung Cancer and Management of Advanced Cancer Pain of Hubei Province, Yichang, China.
  • 10 Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
PMID: 41431124 DOI: 10.1111/jcmm.70968
Abstract

Cervical Cancer remains a leading cause of cancer-related mortality among women worldwide, posing a severe threat to female health. Previous research indicates that Cuproptosis is a copper-dependent form of regulated cell death, holding potential as a therapeutic avenue. This study aimed to identify and validate Cuproptosis-Related Genes (CRGs) as biomarkers and therapeutic targets in cervical Cancer. Transcriptomic data from TCGA and GTEx databases were analysed alongside curated literature data, leading to the identification of 67 pivotal CRGs. Diagnostic and prognostic models were constructed using machine learning algorithms and LASSO-Cox regression, respectively. Glutathione synthetase (GSS) was selected for subsequent functional validation in cellular assays. Drug sensitivity analysis, mechanistic investigations and in vivo experiments were conducted to evaluate therapeutic potential. Statistical analyses were performed using R and GraphPad Prism. Our analysis identified GSS as a core gene. Functional experiments showed that GSS promotes cervical Cancer cell proliferation and invasion under cuproptosis-inducing conditions. Drug sensitivity analysis linked GSS to vorinostat, which inhibits tumour growth by suppressing the PI3K/Akt pathway and downregulating GSS. These findings were confirmed in both in vitro and in vivo studies. This study identifies GSS as a key Cuproptosis regulator and a promising therapeutic target in cervical Cancer, suggesting a novel precision medicine strategy.

Keywords

bioinformatics; cervical cancer; cuproptosis; glutathione synthetase; vorinostat.

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