ArticleProceedings of the National Academy of Sciences of the United States of America2011
The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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104 citing papers in PubMed, 199 citations in OpenAlex.
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- Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.Biomedicines · 2024Review
- PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Alternative therapeutic strategies in diabetes management.World journal of diabetes · 2024Review
- Evaluation of miRNA Expression in Patients with Gestational Diabetes Mellitus: Investigating Diagnostic Potential and Clinical Implications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
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- The role of noncoding RNAs in pancreatic birth defects.Birth defects research · 2023Review
- Genetics of diabetes.World journal of diabetes · 2023Review
- Bone Marrow Mesenchymal Stem Cells-Derived miR-21-5p Protects Grafted Islets Against Apoptosis by Targeting PDCD4.Stem cells (Dayton, Ohio) · 2023Article
- Sex differences in islet stress responses support female β cell resilience.Molecular metabolism · 2023Article
- Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression.Current oncology (Toronto, Ont.) · 2023Article
- Hispidin Inhibits Ferroptosis Induced by High Glucose via the miR-15b-5p/GLS2 Axis in Pancreatic Beta Cells.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Unveiling the Vital Role of Long Non-Coding RNAs in Cardiac Oxidative Stress, Cell Death, and Fibrosis in Diabetic Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Advances in oral peptide drug nanoparticles for diabetes mellitus treatment.Bioactive materials · 2022Review
- MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake.Nature communications · 2022Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Death of pancreatic β cells is a pathological hallmark of type 1 diabetes (T1D). However, the molecular mechanisms of β cell death and its regulation are poorly understood. Here we describe a unique regulatory pathway of β cell death that comprises microRNA-21, its target tumor suppressor PDCD4, and its upstream transcriptional activator nuclear factor-κB (NF-κB). In pancreatic β cells, c-Rel and p65 of the NF-κB family activated the mir21 gene promoter and increased miR-21 RNA levels; miR-21 in turn decreased the level of PDCD4, which is able to induce cell death through the Bax family of apoptotic proteins. Consequently, PDCD4 deficiency in pancreatic β cells renders them resistant to death, and PDCD4 deficiency in NOD or C57BL/6 mice conferred resistance to spontaneous diabetes and diabetes induced by autoimmune T cells or the β cell toxin streptozotocin (STZ). Thus, the NF-κB-microRNA-21-PDCD4 axis plays a crucial role in T1D and represents a unique therapeutic target for treating the disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.