Histone acetyltransferase CSRP2BP promotes the epithelial–mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin
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Le résumé fourni par la source
BACKGROUND: Dysregulated epithelial-mesenchymal transition (EMT) is involved in cervical cancer metastasis and associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive. METHODS: We systematically investigated the expression patterns of histone acetylation genes and their correlations with the EMT pathway in cervical cancer. The expression of CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effects of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were examined by cell growth curve, EdU assay, flow cytometry and xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effects of CSRP2BP on cell invasion and metastasis of cervical cancer cells in vivo and in vitro. RNA-seq, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter assays were used to uncover the molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and metastasis. RESULTS: We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis both in vitro and in vivo, while knockdown of CSRP2BP obtained the opposite effects. In addition, CSRP2BP promoted resistance to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, cooperated with the transcription factor SMAD4 to bind to the SEB2 sequence in the N-cadherin gene promotor and upregulated N-cadherin transcription. Consequently, CSRP2BP promoted cervical cancer cell EMT and metastasis through activating N-cadherin. CONCLUSIONS: This study demonstrates that the histone acetyltransferase CSRP2BP promotes cervical cancer metastasis partially through increasing the EMT and suggests that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Histone acetyltransferase CSRP2BP promotes the epithelial–mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin
- Date Crossref
- 17/10/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Hainan Medical University Hainan Provincial Clinical Research Center for Thalassemia pays non établi dans la noticeUniversité ou école supérieure
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Nanfang Hospital pays non établi dans la noticeÉtablissement de santé
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Southern Medical University Department of Obstetrics and Gynecology pays non établi dans la noticeUniversité ou école supérieure
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East China Normal University pays non établi dans la noticeUniversité ou école supérieure
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Hainan Modern Women and Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Hainan Medical College Hospital pays non établi dans la noticeÉtablissement de santé
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College of Biomedical Information and Engineering pays non établi dans la noticeUniversité ou école supérieure
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Institute of Biomedical Sciences and School of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
Hainan Provincial Clinical Research Center for Thalassemia — Hainan Medical University, Nanfang Hospital et Department of Obstetrics and Gynecology — Southern Medical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.