GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis

Tianfeng Dang1,2,1, Jieqing Yu1,1, Yanqing Yu3

  • 1Jiangxi Otorhinolaryngology-Head and Neck Surgery Institute, Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Insights

Glutathione peroxidase 4 (GPX4) and FKBP8 promote thyroid cancer (TC) by inhibiting apoptosis. Targeting the GPX4/FKBP8/Bcl-2 axis may offer new therapeutic strategies for TC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Glutathione peroxidase 4 (GPX4) is recognized for its role in ferroptosis.
  • The function of GPX4 in apoptosis, particularly in thyroid cancer (TC), remains largely unexplored.
  • FKBP8 is also implicated in cancer progression, but its interplay with GPX4 in TC is not well understood.

Purpose of the Study:

  • To investigate the role of GPX4 and FKBP8 in thyroid cancer cell apoptosis and prognosis.
  • To elucidate the molecular mechanism underlying the GPX4/FKBP8 interaction in TC.
  • To identify potential therapeutic targets for TC based on the GPX4/FKBP8/Bcl-2 axis.

Main Methods:

  • Analysis of TCGA database for GPX4 and FKBP8 expression and correlation with prognosis.
  • Immunohistochemical analysis of GPX4 and FKBP8 in TC tissues.
  • In vivo studies involving tumor growth inhibition by GPX4 silencing.
  • Co-immunoprecipitation assays to confirm GPX4-FKBP8 interaction.
  • Gene silencing and rescue experiments to assess functional roles.

Main Results:

  • GPX4 and FKBP8 were highly expressed in TC tissues and correlated with poor prognosis.
  • GPX4 silencing inhibited TC cell proliferation, induced apoptosis, and reduced tumor growth.
  • GPX4 and FKBP8 physically interact in TC cells.
  • FKBP8 knockdown inhibited proliferation and induced apoptosis, reversing GPX4 overexpression effects.
  • The GPX4/FKBP8/Bcl-2 axis was identified as promoting TC development by inhibiting apoptosis.

Conclusions:

  • The GPX4/FKBP8/Bcl-2 axis plays a critical role in promoting thyroid cancer progression by suppressing apoptosis.
  • GPX4 and FKBP8 represent potential therapeutic targets for developing novel treatment strategies for thyroid cancer.

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