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MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4
Open accessAbstract
Reactive oxygen species (ROS)-induced cardiac cell injury via expression changes of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate about 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. Currently, the effects of ROS on miRNA expression and the roles of miRNAs in ROS-mediated injury on cardiac myocytes are uncertain. Using quantitative real-time RT-PCR (qRT-PCR), we demonstrated that microRNA-21 (miR-21) was upregulated in cardiac myocytes after treatment with hydrogen peroxide (H2O2). To determine the potential roles of miRNAs in H2O2-mediated gene regulation and cellular injury, miR-21 expression was downregulated by miR-21 inhibitor and upregulated by pre-miR-21. H2O2-induced cardiac cell death and apoptosis were increased by miR-21 inhibitor and was decreased by pre-miR-21. Programmed cell death 4 (PDCD4) that was regulated by miR-21 and was a direct target of miR-21 in cardiac myocytes. Pre-miR-21-mediated protective effect on cardiac myocyte injury was inhibited in H2O2-treated cardiac cells via adenovirus-mediated overexpression of PDCD4 without miR-21 binding site. Moreover, Activator protein 1 (AP-1) was a downstream signaling molecule of PDCD4 that was involved in miR-21-mediated effect on cardiac myocytes. The results suggest that miR-21 is sensitive to H2O2 stimulation. miR-21 participates in H2O2-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.
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“For example, miR-21 protects cardiomyocytes against H2O2 induced cell apoptosis by targeting the proapoptotic proteins PDCD437.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [37]
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“Cheng et al. have shown that miR-21 is upregulated in response to H2O2 injury in cardiac myocytes, and that it functions to attenuate apoptosis in that cell population [29].”
From MicroRNA‐21 protects neurons from ischemic death (2010) · cites this paper as [29]
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Metadata
- Authors
- Cheng, Y., Liu, X., Zhang, S., Lin, Y., Yang, J., & Zhang, C.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Zhang, Chunxiang
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 47
- Issue
- 1
- Pages
- 5-14
- ISSN
- 0022-2828 (ISSN-L)
- PMC
- PMC3593965
- OpenAlex
- W2141570739
- Semantic Scholar
- 1fbe4e1a56db9230d95dce535ef1d9e12a4d760a
- Cited by
- 368
- References
- 36
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 11 · 2022: 16 · 2021: 20 · 2020: 24 · 2019: 25 · 2018: 23 · 2017: 18 · 2016: 29 · 2015: 23 · 2014: 26 · 2013: 28 · 2012: 29
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 080133, R01HL095707, R01HL080133)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- miR-21, PDCD4, hydrogen peroxide, reactive oxygen species, cardiomyocytes, oxidative stress, apoptosis, cardioprotection, AP-1, microRNA target regulation, heart disease
- MeSH terms
- Animals, Hydrogen Peroxide, Necrosis, Blotting, Western, Rats, Sprague-Dawley, Apoptosis, Transcription Factor AP-1, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Cardiac, MicroRNAs, Apoptosis Regulatory Proteins, Rats
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