A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress
The integrated stress response (ISR) is a key regulator of cell survival, promoting apoptosis through the effector protein CHOP in instances of prolonged or severe stress. The ISR’s role in the initiation and progression of epithelial malignancies has been investigated; however, the ISR has not been...
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2025-05-01
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| author | Isabella Boyack Autumn Berlied Cornelia Peterson |
| author_facet | Isabella Boyack Autumn Berlied Cornelia Peterson |
| author_sort | Isabella Boyack |
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| description | The integrated stress response (ISR) is a key regulator of cell survival, promoting apoptosis through the effector protein CHOP in instances of prolonged or severe stress. The ISR’s role in the initiation and progression of epithelial malignancies has been investigated; however, the ISR has not been evaluated in ocular adnexal sebaceous carcinoma (SebCA). Though uncommon, mortality rates of up to 40% have been reported, and the mechanisms underlying SebCA tumorigenesis remain unresolved; however, <i>c-MYC</i> upregulation has been documented. Our objective was to determine the role of MYC in modulating the ISR in the Meibomian gland. Human Meibomian gland epithelial cells (HMGECs) were subject to both pharmacologic and genetic manipulations of MYC expression. Cytotoxicity, proliferation, and changes in protein and gene expression were assessed. Conditionally <i>MYC</i>-overexpressing mice were subject to topical 4-hydroxytamoxifen (4-OHT) induction of the eyelids prior to tissue harvest for histology, immunohistochemistry, immunoblotting, and qPCR. MYC-inhibited HMGECs exhibited dose-dependent decreased proliferation, increased CHOP expression, and increased apoptosis. Conversely, <i>MYC</i>-overexpressing HMGECs and Meibomian glands from 4-OHT-induced mice demonstrated suppressed CHOP expression, reduced apoptosis, and upregulated fatty acid synthase expression. These results suggest that MYC inhibition induces the ISR and promotes apoptosis, while MYC induction suppresses CHOP expression. High MYC expression may, therefore, serve as a mechanism for SebCA to elude cell death by promoting lipogenesis. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-bb1d7d10c5e34c3eba9a3241f3ba5e9d2025-08-20T03:47:53ZengMDPI AGCells2073-44092025-05-01141070910.3390/cells14100709A Potential Role for c-MYC in the Regulation of Meibocyte Cell StressIsabella Boyack0Autumn Berlied1Cornelia Peterson2Department of Comparative Pathobiology, Tufts University, North Grafton, MA 01536, USADepartment of Comparative Pathobiology, Tufts University, North Grafton, MA 01536, USADepartment of Comparative Pathobiology, Tufts University, North Grafton, MA 01536, USAThe integrated stress response (ISR) is a key regulator of cell survival, promoting apoptosis through the effector protein CHOP in instances of prolonged or severe stress. The ISR’s role in the initiation and progression of epithelial malignancies has been investigated; however, the ISR has not been evaluated in ocular adnexal sebaceous carcinoma (SebCA). Though uncommon, mortality rates of up to 40% have been reported, and the mechanisms underlying SebCA tumorigenesis remain unresolved; however, <i>c-MYC</i> upregulation has been documented. Our objective was to determine the role of MYC in modulating the ISR in the Meibomian gland. Human Meibomian gland epithelial cells (HMGECs) were subject to both pharmacologic and genetic manipulations of MYC expression. Cytotoxicity, proliferation, and changes in protein and gene expression were assessed. Conditionally <i>MYC</i>-overexpressing mice were subject to topical 4-hydroxytamoxifen (4-OHT) induction of the eyelids prior to tissue harvest for histology, immunohistochemistry, immunoblotting, and qPCR. MYC-inhibited HMGECs exhibited dose-dependent decreased proliferation, increased CHOP expression, and increased apoptosis. Conversely, <i>MYC</i>-overexpressing HMGECs and Meibomian glands from 4-OHT-induced mice demonstrated suppressed CHOP expression, reduced apoptosis, and upregulated fatty acid synthase expression. These results suggest that MYC inhibition induces the ISR and promotes apoptosis, while MYC induction suppresses CHOP expression. High MYC expression may, therefore, serve as a mechanism for SebCA to elude cell death by promoting lipogenesis.https://www.mdpi.com/2073-4409/14/10/709Meibomian gland epithelial cellssebaceous carcinomaMYCintegrated stress responseCHOPapoptosis |
| spellingShingle | Isabella Boyack Autumn Berlied Cornelia Peterson A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress Cells Meibomian gland epithelial cells sebaceous carcinoma MYC integrated stress response CHOP apoptosis |
| title | A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress |
| title_full | A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress |
| title_fullStr | A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress |
| title_full_unstemmed | A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress |
| title_short | A Potential Role for c-MYC in the Regulation of Meibocyte Cell Stress |
| title_sort | potential role for c myc in the regulation of meibocyte cell stress |
| topic | Meibomian gland epithelial cells sebaceous carcinoma MYC integrated stress response CHOP apoptosis |
| url | https://www.mdpi.com/2073-4409/14/10/709 |
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