ArticleDiabetologia2017
MicroRNA 21 targets BCL2 mRNA to increase apoptosis in rat and human beta cells.
Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 99 citations in OpenAlex.
- From In Silico to Clinic: Harnessing Noncoding RNAs for Diabetes Research and Therapy, a Step toward ncRNA Precision.ACS pharmacology & translational science · 2026Review
- Beta cell microRNAs function as molecular hubs of type 1 diabetes pathogenesis and as biomarkers of diabetes risk.Diabetologia · 2026Article
- Unlocking beta cell health: The clinical potential of extracellular vesicles in type 1 diabetes.Clinical and translational medicine · 2026Review
- Knowledge gaps and research priorities to understand sex differences in immunity.PLoS biology · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Proinflammatory Stress Activates Neutral Sphingomyelinase 2-Based Generation of a Ceramide-Enriched β-Cell EV Subpopulation.Diabetes · 2025Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025Review
- Enhanced anticancer efficacy of aluminum-curcumin complex compared to curcumin in colorectal cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- miRNA-642a-3p protects β cells from glucolipotoxicity.Molecular therapy. Nucleic acids · 2025Article
- microRNAs in Type 1 Diabetes: Roles, Pathological Mechanisms, and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Biochemical, histological, and immunohistochemical study on the therapeutic effects and mechanism of coenzyme QResearch in pharmaceutical sciences · 2025Article
- iModEst: disentangling -omic impacts on gene expression variation across genes and tissues.NAR genomics and bioinformatics · 2025Article
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- miRNA-21, an Important Regulator of Autoimmune Diseases.Current molecular medicine · 2025Review
- Review
- The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.International journal of molecular sciences · 2024Review
- miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis.The Journal of biological chemistry · 2024Article
- Review
- Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.Biomedicines · 2024Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe role of beta cell microRNA (miR)-21 in the pathophysiology of type 1 diabetes has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in type 1 diabetes and the phenotype of beta cell miR-21 overexpression through target identification.
methodsIslets were isolated from NOD mice and mice treated with multiple low doses of streptozotocin, as a mouse model of diabetes. INS-1 832/13 beta cells and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the milieu of early type 1 diabetes. Cells and islets were transfected with miR-21 mimics or inhibitors. Luciferase assays and polyribosomal profiling (PRP) were performed to define miR-21-target interactions.
resultsBeta cell miR-21 was increased in in vivo models of type 1 diabetes and cytokine-treated cells/islets. miR-21 overexpression decreased cell count and viability, and increased cleaved caspase 3 levels, suggesting increased cell death. In silico prediction tools identified the antiapoptotic mRNA BCL2 as a conserved miR-21 target. Consistent with this, miR-21 overexpression decreased BCL2 transcript and B cell lymphoma 2 (BCL2) protein production, while miR-21 inhibition increased BCL2 protein levels and reduced cleaved caspase 3 levels after cytokine treatment. miR-21-mediated cell death was abrogated in 828/33 cells, which constitutively overexpress Bcl2. Luciferase assays suggested a direct interaction between miR-21 and the BCL2 3' untranslated region. With miR-21 overexpression, PRP revealed a shift of the Bcl2 message towards monosome-associated fractions, indicating inhibition of Bcl2 translation. Finally, overexpression in dispersed human islets confirmed a reduction in BCL2 transcripts and increased cleaved caspase 3 production. CONCLUSIONS/
interpretationIn contrast to the pro-survival role reported in other systems, our results demonstrate that miR-21 increases beta cell death via BCL2 transcript degradation and inhibition of BCL2 translation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.