PPP3CB inhibits pancreatic cancer progression by promoting ATOH8 translocation and transcriptionally regulating Sp1
Rattachement africain : cn, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy which lacks effective therapeutic targets. We previously demonstrated that low PPP3CB expression correlates with poor prognosis in PDAC. This study aims to investigate the function and underlying mechanism of PPP3CB in pancreatic cancer progression. MATERIALS AND METHODS: We analyzed PPP3CB expression via immunohistochemistry in PDAC specimens and investigated its prognostic value by statistical method. Differentially expressed genes were analyzed by qRT-PCR and Western blot. Mass spectrometry, Co-IP, ChIP-seq, luciferase analysis, flow cytometry, immunofluorescence and confocal microscopy were performed to investigate the underlying mechanisms of PPP3CB and regulation of ATOH8/Sp1 axis. Mice xenograft models were employed to assess the malignant behaviors in vivo. KEY FINDINGS: We found that PPP3CB expression was higher in patients with early-stage PDAC than in those with late-stage PDAC. PPP3CB overexpression impaired PDAC proliferation and metastasis in vitro and in vivo, whereas its depletion or treatment with CsA-a PPP3CB inhibitor, had the opposite effect. Liquid chromatography-tandem mass spectrometry predicted an interaction between PPP3CB and ATOH8. Further investigation confirmed that PPP3CB interacts with ATOH8 and enhances its nuclear translocation in PDAC cells. ChIP-seq and luciferase analyses showed that ATOH8 binds to the promoter of Sp1, a well-known oncogenic transcription factor in PDAC. Furthermore, PPP3CB transcriptionally inhibits Sp1 expression and suppresses pancreatic cancer metastases by increasing ATOH8 nuclear content. SIGNIFICANCE: These findings suggest a novel role for PPP3CB in preventing PDAC progression by promoting ATOH8 nuclear translocation and transcriptionally inhibiting Sp1. Consequently, PPP3CB emerges as a potential therapeutic target for PDAC.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- PPP3CB inhibits pancreatic cancer progression by promoting ATOH8 translocation and transcriptionally regulating Sp1
- Date Crossref
- 01/07/2025
- Éditeur
- Elsevier BV
- 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
-
Shanghai Jiao Tong University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
-
Shanghai First People's Hospital pays non établi dans la noticeÉtablissement de santé
-
Shanghai Zhabei District Shibei Hospital pays non établi dans la noticeÉtablissement de santé
-
Sun Yat-sen University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
-
Fifth Affiliated Hospital of Sun Yat-sen University pays non établi dans la noticeÉtablissement de santé
-
Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
-
Renji Hospital pays non établi dans la noticeÉtablissement de santé
-
Shanghai Cancer Institute pays non établi dans la noticeStructure de recherche
-
State Key Laboratory of Oncogene and Related Genes pays non établi dans la noticeStructure de recherche
-
National Cancer Center pays non établi dans la noticeOrganisation à but non lucratif
-
Shanghai JingAn District ZhaBei Central Hospital Department of Oncology pays non établi dans la noticeÉtablissement de santé
-
Chinese Academy of Medical Sciences and Peking Union Medical College National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital pays non établi dans la noticeUniversité ou école supérieure
Department of Oncology — Shanghai Jiao Tong University, Shanghai First People's Hospital et Shanghai Zhabei District Shibei Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.