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Published on: February 27, 2016
SIRT7 deficiency promoted cuproptosis-mediated mitochondrial dysfunction and inhibited malignant development of
Qun Gao1, Qi Wang2, Yanjiao Hu3
1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.
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.
Insights
Sirtuin 7 (SIRT7) acts as an oncogene in cervical cancer, promoting tumor growth and inhibiting cuproptosis. Downregulation of SIRT7 triggers cuproptosis, halting cancer cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cervical cancer remains a significant global health challenge.
- Understanding the molecular mechanisms driving cervical cancer progression is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate the role of Sirtuin 7 (SIRT7) in cervical cancer development.
- To investigate the interplay between SIRT7 and cuproptosis in cervical cancer cells.
Main Methods:
- SIRT7 overexpression and knockdown were performed in HeLa and SiHa cells.
- Cell proliferation, apoptosis, invasion, and migration were assessed using various assays.
- Cuproptosis was analyzed through copper ion content, mitochondrial function, reactive oxygen species (ROS) levels, and related protein expression, utilizing inhibitors and activators.
Main Results:
- SIRT7 overexpression enhanced cervical cancer cell proliferation, migration, and invasion while inhibiting apoptosis.
- SIRT7 knockdown induced cuproptosis, characterized by increased copper levels, mitochondrial dysfunction, elevated ROS, and altered expression of cuproptosis-related proteins.
- SIRT7's influence on cuproptosis was modulated by copper levels and specific inhibitors/activators.
Conclusions:
- SIRT7 functions as an oncogene in cervical cancer, promoting tumor growth by enhancing proliferation and invasion.
- SIRT7 suppresses cuproptosis, and its downregulation activates this cell death pathway, thereby inhibiting tumor progression.
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