NPR1 promotes cisplatin resistance by inhibiting PARL-mediated mitophagy-dependent ferroptosis in gastric cancer
Rattachement africain : cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Cisplatin-based chemotherapy serves as the standard of care for individuals with advanced stages of gastric cancer. Nevertheless, the emergence of chemoresistance in GC has detrimental impacts on prognosis, yet the underlying mechanisms governing this phenomenon remain elusive. Level of mitophagy and ferroptosis of GC cells were detected by fluorescence, flow cytometry, GSH, MDA, Fe2+ assays, and to explore the specific molecular mechanisms between NPR1 and cisplatin resistance by performing western blot and coimmunoprecipitation (co-IP) assays. These results indicates that NPR1 positively correlated with cisplatin-resistance and played a crucial part in conferring resistance to cisplatin in gastric cancer cells. Mechanistically, NPR1 affected levels of mitophagy and ferroptosis in human cisplatin-resistance GC cells with cisplatin treatment. Specifically, NPR1 inhibited mitophagy-dependent ferroptosis by reducing the ubiquitination-mediated degradation of PARL; moreover, NPR1 promoted PARL stabilization by disrupting the PARL–MARCH8 complex, which ultimately led to the development of chemoresistance in GC cells. Considering our findings, NPR1 appears to play an important role in chemotherapy for GC. NPR1 could potentially be used to overcome chemotherapy resistance. 1. NPR1 is highly expressed in cisplatin-resistant GC cells and promotes the cisplatin resistance. 2. According to IP-MS, NPR1 inhibits mitophagy-dependent ferroptosis through its downstream protein PARL. 3. NPR1 promoted PARL stabilization by disrupting the PARL–MARCH8 complex to inhibit the ubiquitination-mediated degradation of PARL.
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
- NPR1 promotes cisplatin resistance by inhibiting PARL-mediated mitophagy-dependent ferroptosis in gastric cancer
- Date Crossref
- 30/10/2024
- 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
-
First Affiliated Hospital of Wannan Medical College pays non établi dans la noticeÉtablissement de santé
-
Fudan University pays non établi dans la noticeUniversité ou école supérieure
-
Anhui Xinhua University pays non établi dans la noticeUniversité ou école supérieure
-
Anhui Province Key Laboratory of Non-Coding RNA Basic and Clinical Transformation pays non établi dans la noticeStructure de recherche
-
Yijishan Hospital of Wannan Medical College Department of Gastrointestinal Surgery pays non établi dans la noticeUniversité ou école supérieure
-
School of Basic Medical Sciences Department of Immunology pays non établi dans la noticeUniversité ou école supérieure
First Affiliated Hospital of Wannan Medical College, Fudan University et Anhui Xinhua University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.