Articles
Vol. 69 No. 3 (2025)
NR4A3 suppresses bladder cancer progression by modulating autophagy via the PI3K/AKT/mTOR pathway
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 30 June 2025
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Bladder cancer (BC) is a prevalent and aggressive malignancy with high recurrence. Autophagy plays a dual role in cancer, acting as a tumor suppressor early on and promoting survival in later stages. NR4A3, a nuclear receptor with tumor-suppressive effects in other cancers, has not been explored in BC. NR4A3 expression was analyzed using TCGA data and validated in clinical BC samples via immunohistochemistry and RT-qPCR. NR4A3-overexpressing BC cell lines (5637, T24) were created using lentiviral vectors. Cell viability, proliferation, migration, and invasion were assessed through CCK-8, EdU, and Transwell assays. Autophagy was measured by microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related protein 5 (ATG5), Beclin-1 and p62 expression via immunofluorescence and Western blotting. The phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway was examined by assessing phosphorylation levels. It was found that NR4A3 was significantly downregulated in BC tissues. Overexpression of NR4A3 inhibited BC cell proliferation, migration, and invasion, while promoting apoptosis. NR4A3 overexpression increased autophagy markers and suppressed PI3K/AKT/mTOR signaling. Autophagy inhibition reversed these effects. In conclusion, NR4A3 suppresses BC progression by promoting autophagy via the PI3K/AKT/mTOR pathway. Targeting NR4A3-mediated autophagy may provide a novel therapeutic strategy for BC.
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Ethics Approval
The experimental protocols in this study were approved by the Clinical Ethics Committee of PLA Eastern Theater Command General HospitalHow to Cite
1.
Fan L, Xu F, Liu S, Wu D, Wang S, Pan X, et al. NR4A3 suppresses bladder cancer progression by modulating autophagy via the PI3K/AKT/mTOR pathway. Eur J Histochem [Internet]. 2025 Jun. 30 [cited 2026 Jan. 20];69(3). Available from: https://www.ejh.it/ejh/article/view/4221
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