ArticleJournal of geriatric cardiology : JGC2021
MiR-21-5p-expressing bone marrow mesenchymal stem cells alleviate myocardial ischemia/reperfusion injury by regulating the circRNA_0031672/miR-21-5p/programmed cell death protein 4 pathway.
Article in Journal of geriatric cardiology : JGC, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Programmed cell death protein 4 (PDCD4): a pleiotropic regulator in cardiovascular diseases.Journal of physiology and biochemistry · 2026Review
- Association between potassium fluctuation and in-hospital mortality in acute myocardial infarction patients: a retrospective analysis of the MIMIC-IV database.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- Non-coding RNA biomarkers in resistant hypertension: a scoping review.Frontiers in molecular biosciences · 2026Review
- Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics.Scientific reports · 2025Article
- Serum Expression of PDCD4 and ADAM10 in Elderly Patients with Atherosclerotic Acute Myocardial Infarction and Their Combined Predictive Value for Poor Prognosis.Clinical interventions in aging · 2025Article
- CircRNA Networks in CAD: Multi-Cellular Mechanisms and Clinical Potential.International journal of general medicine · 2025Review
- CircRNA-mediated regulation of cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Mesenchymal Stem Cell-Derived Exosomal Noncoding RNAs as Alternative Treatments for Myocardial Ischemia-Reperfusion Injury: Current Status and Future Perspectives.Journal of cardiovascular translational research · 2023Review
- MiR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression.Bioscience reports · 2023Article
- The Landscape of Circular RNAs in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- Article
- Circular RNAs Acting as miRNAs' Sponges and Their Roles in Stem Cells.Journal of clinical medicine · 2022Review
- Construction of the ceRNA network in the progression of acute myocardial infarction.American journal of cardiovascular disease · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFor patients with coronary heart disease, reperfusion treatment strategies are often complicated by ischemia/reperfusion (I/R) injury (IRI), leading to serious organ damage and malfunction. The miR-21/programmed cell death protein 4 (PDCD4) pathway is involved in the IRI of cardiomyocytes; however, the aberrant miR-21 expression remains unexplained. Therefore, this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to determine whether miR-21-5p-expressing bone marrow mesenchymal stem cells (BMSCs) reduce myocardial IRI.
methodsCircRNA_0031672, miR-21-5p, and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxygenation (H/R)-treated H9C2 cells. Their interactions were subsequently investigated using luciferase reporter and RNA pulldown assays. Methyltransferase-like 3, a methyltransferase catalyzing N6-methyladenosine (m6A), was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4. BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R.
resultsI/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions. CircRNA_0031672 knockdown increased miR-21-5p expression, but repressed PDCD4 expression, indicating that circRNA_0031672 competitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA. The m6A modification regulated PDCD4 expression, but had no effect on miR-21-5p targeting PDCD4. The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment; co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R.
conclusionsWe identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs, offering novel insights into the IRI pathogenesis in cardiovascular diseases.
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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.