Phosphodiesterase 1A physically interacts with YTHDF2 and reinforces the progression of non-small cell lung cancer
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Le résumé fourni par la source
Abstract Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and the prognosis is poor due to distant metastasis and drug resistance. Thus, there is an urgent need to discover novel therapeutic targets and strategies to overcome cisplatin resistance and metastasis. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of PDE1A in NSCLC. The RIP assay, mRNA stability assay and LC- MS/MS were performed to investigate the molecular mechanisms of PDE1A in NSCLC progression. We demonstrated that phosphodiesterase 1A (PDE1A) promoted metastasis and EMT progression of NSCLC. In addition, NSCLC cells overexpressing PDE1A promoted angiogenesis by regulating exosome release. IL-6/JAK/STAT3 signaling pathway was highly enriched in PDE1A- coexpresssed genes, and PDE1A promoted NSCLC metastasis by activating the STAT3 pathway. GO enrichment analysis of PDE1A-interacting genes showed that PDE1A might interact with YTHDF2 and participate in m6A- containing RNA binding. The binding between PDE1A and YTHDF2 was verified, and PDE1A regulated the STAT3 pathway by interacting with YTHDF2. The mechanism of YTHDF2/PDE1A complex in regulating STAT3 pathway was predicted by overlapping YTHDF2-interacting-RNAs, and genes coexpressed with YTHDF2 and STAT3. The interactions between YTHDF2 and target mRNAs were predicted, and there were three predicted targets of YTHDF2 with high scores: NRF2, SOCS2, and MET. Indeed, PDE1A interacted with YTHDF2, destabilized SOCS2, and activated STAT3 pathway. Moreover, PDE1A suppression sensitized anti-NSCLC activity of cisplatin via regulating NRF2 and MET. This work not only uncovers a novel PDE1A/YTHDF2/STAT3 pathway in NSCLC progression but also provides therapeutic strategies for treating NSCLC patients with metastasis or cisplatin- resistance.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Phosphodiesterase 1A physically interacts with YTHDF2 and reinforces the progression of non-small cell lung cancer
- Date Crossref
- 15/10/2024
- Éditeur
- eLife Sciences Publications, Ltd
- Type
- posted-content
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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City University pays non établi dans la noticeUniversité ou école supérieure
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Hangzhou City University pays non établi dans la noticeUniversité ou école supérieure
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Ningbo First Hospital Department of Pharmacy pays non établi dans la noticeÉtablissement de santé
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Wenzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang University Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang University of Technology pays non établi dans la noticeUniversité ou école supérieure
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Westlake University Affiliated Hangzhou First People's Hospital pays non établi dans la noticeÉtablissement de santé
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School of Medicine Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Shangyu People’s Hospital of Shaoxing Department of oncology pays non établi dans la noticeÉtablissement de santé
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The Affiliated Hospital of Northwest University · XI’AN NO.3 Hospital Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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College of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
City University, Hangzhou City University et Department of Pharmacy — Ningbo First Hospital, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.