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.

Abstract

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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