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.
Abstract:
GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.
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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