ArticleJournal of cellular physiology2018
MicroRNA501-5p induces p53 proteasome degradation through the activation of the mTOR/MDM2 pathway in ADPKD cells.
Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- The Renal Micro-RNA Expression Profile of Pkd1RC/RC Mice Changes Longitudinally with the Progression of the Disease.Kidney360 · 2026Article
- Sodium-Glucose Cotransporter 2 Inhibitors in Autosomal Dominant Polycystic Kidney Disease: Mechanistic Insights and Therapeutic Promise.Journal of the American Society of Nephrology : JASN · 2026Review
- Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease-The Promised Land?Medicina (Kaunas, Lithuania) · 2023Review
- Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease.Frontiers in physiology · 2022Review
- Recent Discoveries in Epigenetic Modifications of Polycystic Kidney Disease.International journal of molecular sciences · 2021Review
- NS398 as a potential drug for autosomal-dominant polycystic kidney disease: Analysis using bioinformatics, and zebrafish and mouse models.Journal of cellular and molecular medicine · 2021Article
- Non-Coding RNAs in Hereditary Kidney Disorders.International journal of molecular sciences · 2021Review
- miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1.Renal failure · 2020Article
- Perivascular epithelioid cell tumor (PEComa) of the kidney: an overview of its management and outcomes.The Journal of international medical research · 2020Article
- Targeting MDM2 for novel molecular therapy: Beyond oncology.Medicinal research reviews · 2020Review
- Degradation of proteins by PROTACs and other strategies.Acta pharmaceutica Sinica. B · 2020Review
- Identification of housekeeping genes for microRNA expression analysis in kidney tissues of Pkd1 deficient mouse models.Scientific reports · 2020Article
- Systems biology approaches toward autosomal dominant polycystic kidney disease (ADPKD).Clinical and translational medicine · 2020Article
- TRPP2 dysfunction decreases ATP-evoked calcium, induces cell aggregation and stimulates proliferation in T lymphocytes.BMC nephrology · 2019Article
- Role of PKR in the Inhibition of Proliferation and Translation by Polycystin-1.BioMed research international · 2019Article
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- MicroRNAs and Polycystic Kidney Disease.Kidney medicineReview
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Cell proliferation and apoptosis are typical hallmarks of autosomal dominant polycystic kidney disease (ADPKD) and cause the development of kidney cysts that lead to end-stage renal disease (ESRD). Many factors, impaired by polycystin complex loss of function, may promote these biological processes, including cAMP, mTOR, and EGFR signaling pathways. In addition, microRNAs (miRs) may also regulate the ADPKD related signaling network and their dysregulation contributes to disease progression. However, the role of miRs in ADPKD pathogenesis has not been fully understood, but also the function of p53 is quite obscure, especially its regulatory contribution on cell proliferation and apoptosis. Here, we describe for the first time that miR501-5p, upregulated in ADPKD cells and tissues, induces the activation of mTOR kinase by PTEN and TSC1 gene repression. The increased activity of mTOR kinase enhances the expression of E3 ubiquitin ligase MDM2 that in turn promotes p53 ubiquitination, leading to its degradation by proteasome machinery in a network involving p70S6K. Moreover, the overexpression of miR501-5p stimulates cell proliferation in kidney cells by the inhibition of p53 function in a mechanism driven by mTOR signaling. In fact, the downregulation of this miR as well as the pharmacological treatment with proteasome and mTOR inhibitors in ADPKD cells reduces cell growth by the activation of apoptosis. Consequently, the stimulation of cell death in ADPKD cells may occur through the inhibition of mTOR/MDM2 signaling and the restoring of p53 function. The data presented here confirm that the impaired mTOR signaling plays an important role in ADPKD.
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Registered trials
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