Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer
Abstract Background Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. Methods The protein leve...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04141-3 |
| _version_ | 1797831930876526592 |
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| author | Xu Xu Xiaona Wang Qihui Chen Aman Zheng Donglu Li Ziqi Meng Xinran Li Hanchen Cai Wangzhi Li Shiyuan Huang Fan Wang |
| author_facet | Xu Xu Xiaona Wang Qihui Chen Aman Zheng Donglu Li Ziqi Meng Xinran Li Hanchen Cai Wangzhi Li Shiyuan Huang Fan Wang |
| author_sort | Xu Xu |
| collection | DOAJ |
| description | Abstract Background Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. Methods The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. Results Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. Conclusions Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer. |
| first_indexed | 2024-04-09T13:59:35Z |
| format | Article |
| id | doaj.art-07cdab0a56264d5cb02efef72c5755a7 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T13:59:35Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-07cdab0a56264d5cb02efef72c5755a72023-05-07T11:22:13ZengBMCJournal of Translational Medicine1479-58762023-05-0121111610.1186/s12967-023-04141-3Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancerXu Xu0Xiaona Wang1Qihui Chen2Aman Zheng3Donglu Li4Ziqi Meng5Xinran Li6Hanchen Cai7Wangzhi Li8Shiyuan Huang9Fan Wang10Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversitySchool of Stomatology, Wenzhou Medical UniversityDepartment of Neurological Rehabilitation, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityAbstract Background Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. Methods The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. Results Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. Conclusions Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.https://doi.org/10.1186/s12967-023-04141-3Specificity protein 1 (Sp1)Mitochondrial networkGlycolysisCervical cancer |
| spellingShingle | Xu Xu Xiaona Wang Qihui Chen Aman Zheng Donglu Li Ziqi Meng Xinran Li Hanchen Cai Wangzhi Li Shiyuan Huang Fan Wang Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer Journal of Translational Medicine Specificity protein 1 (Sp1) Mitochondrial network Glycolysis Cervical cancer |
| title | Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| title_full | Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| title_fullStr | Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| title_full_unstemmed | Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| title_short | Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| title_sort | sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer |
| topic | Specificity protein 1 (Sp1) Mitochondrial network Glycolysis Cervical cancer |
| url | https://doi.org/10.1186/s12967-023-04141-3 |
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