2. Academic Validation
  3. SIRT7 deficiency promoted cuproptosis-mediated mitochondrial dysfunction and inhibited malignant development of cervical cancer

SIRT7 deficiency promoted cuproptosis-mediated mitochondrial dysfunction and inhibited malignant development of cervical cancer

  • Arch Biochem Biophys. 2025 Oct 29:775:110651. doi: 10.1016/j.abb.2025.110651.
Qun Gao 1,  Qi Wang 2,  Yanjiao Hu 3,  Fangjie Xin 3,  Jie Chen 4,  Sha Yu 4,  Xinli Chen 1,  Qingqing Lv 4,  Baoxia Cui 1,  Jun Jiao 5,  Xinlin Jiao 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 3 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • 4 Department of Obstertrics, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • 5 Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University (Qingdao), Jinan, China. Electronic address: jiaojun206@163.com.
  • 6 Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China. Electronic address: jiaoxinlin2211@163.com.
PMID: 41167446 DOI: 10.1016/j.abb.2025.110651
Abstract

Purpose: To investigate the impact of SIRT7 on the development of cervical Cancer and its relationship with Cuproptosis in cervical Cancer.

Method: HeLa and SiHa cells were transfected with lentiviruses for SIRT7 overexpression and knockdown. The effects of SIRT7 on cervical Cancer cell proliferation, Apoptosis, invasion, and migration were analyzed using CCK8, plate cloning, flow cytometry, Transwell assays, and scratch assays. To verify the relationship between SIRT7 and Cuproptosis, we utilized Cuproptosis inhibitors and activators. Immunofluorescence, transmission electron microscope, flow cytometry, ELISA, and Western blot were used to analyze copper ion content, mitochondrial ultrastructure, cellular Reactive Oxygen Species, mitochondrial membrane potential, pyruvate levels, cell viability and the cuproptosis-related proteins.

Results: SIRT7 enhanced the proliferation, migration, and invasion of HeLa and SiHa cells, inhibited Apoptosis, and promoted cervical Cancer growth. Knocking down SIRT7 caused Cuproptosis of HeLa and SiHa cells, characterized by increased Cu2+ content, disrupted mitochondrial structure, decreased membrane potential, elevated ROS production, and upregulation of cuproptosis-related proteins SLC31A1 and HSP70, and downregulation of FDX1, LIAS and DLAT. Low SIRT7 expression's effect on Cuproptosis was reduced by TTM. SIRT7 overexpression inhibited Cuproptosis, unlike SIRT7 knockdown. SIRT7 overexpression's inhibitory effect on Cuproptosis is altered by rhSLC31A1.

Conclusion: SIRT7 was recognized as an oncogene in cervical Cancer, which boosted cervical Cancer cell proliferation and invasion, lowered intracellular copper levels, and prevented Cuproptosis. SIRT7 downregulation triggered Cuproptosis, inhibiting tumor cell growth.

Keywords

Cervical cancer; Cuproptosis; Mitochondrial dysfunction; SIRT7.

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