Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients
Abstract Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-03-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-01899-3 |
| _version_ | 1797259471779528704 |
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| author | Tianming Wang Min Gong Yingfei Lu Chengcheng Zhao Ling Ling Jianquan Chen Rong Ju |
| author_facet | Tianming Wang Min Gong Yingfei Lu Chengcheng Zhao Ling Ling Jianquan Chen Rong Ju |
| author_sort | Tianming Wang |
| collection | DOAJ |
| description | Abstract Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC. |
| first_indexed | 2024-04-24T23:09:58Z |
| format | Article |
| id | doaj.art-0a8e49beea254e00bb142d53fa16a413 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-24T23:09:58Z |
| publishDate | 2024-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-0a8e49beea254e00bb142d53fa16a4132024-03-17T12:14:35ZengNature Publishing GroupCell Death Discovery2058-77162024-03-0110111110.1038/s41420-024-01899-3Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patientsTianming Wang0Min Gong1Yingfei Lu2Chengcheng Zhao3Ling Ling4Jianquan Chen5Rong Ju6Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical UniversityDepartment of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical UniversityCentral Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical UniversityCentral Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical UniversityDepartment of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical UniversityCentral Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical UniversityDepartment of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical UniversityAbstract Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.https://doi.org/10.1038/s41420-024-01899-3 |
| spellingShingle | Tianming Wang Min Gong Yingfei Lu Chengcheng Zhao Ling Ling Jianquan Chen Rong Ju Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients Cell Death Discovery |
| title | Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients |
| title_full | Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients |
| title_fullStr | Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients |
| title_full_unstemmed | Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients |
| title_short | Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients |
| title_sort | oxysterol 25 hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in hpv positive patients |
| url | https://doi.org/10.1038/s41420-024-01899-3 |
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