MiR-21 attenuates apoptosis-triggered by amyloid-β via modulating PDCD4/ PI3K/AKT/GSK-3β pathway in SH-SY5Y cells
Open accessAbstract
Alzheimer's disease (AD) remains the most common neurodegenerative disease with amyloid beta (Aβ) formatted and accumulated. Recently, microRNAs have been identified as significant regulators in neurogenesis of the central nervous system (CNS). However, the biological role of miR-21 in AD remains unclear. The purpose of our study was to investigate the mechanism of miR-21 in AD. AD model was established using 20 μM Aβ 1-42 in SH-SY5Y cells. Aβ 1-42 can induce cell apoptosis via increasing Bax and decreasing Bcl-2 protein levels. Meanwhile, we observed that miR-21 was remarkably elevated by indicated Aβ 1-42 in vitro. Subsequently, miR-21 mimics were transfected into SH-SY5Y cells and it was found that miR-21 can inhibit cell apoptosis induced by Aβ 1-42 . Programmed cell death protein 4 (PDCD4), an important tumor suppressor in various cancers has been reported to prevent AKT activation. The phosphatidylinositol 3-kinase (PI3K)/AKT/GSK-3β pathway can release a survival signal to protect from multiple injuries. Interestingly, it was found that PDCD4 was involved in miR-21-repressed cell apoptosis in AD models. miR-21 mimics can increase the PI3K, AKT and GSK-3β activity while PDCD4 ovexexpression inhibited their activity respectively. Moreover, knockdown of PDCD4 can rescue PI3K/AKT/GSK-3β pathway in SH-SY5Y cells. Taken these together, it was suggested by our data that miR-21 can exert protective roles in AD, which might be dependent on PDCD4/PI3K/AKT/GSK-3β signaling pathway…
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miR-21 was suggested to have both harmful and beneficial effects.
“Despite its nonspecificity [33], miR-21 is considered a versatile regulator in the progression of CNS disorders [34] and was suggested to have both harmful and beneficial effects [35,36,37].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [35]
miR-21 plays an important role in AD neurons by moderating their apoptosis upon Aβ exposure.
“Earlier studies similarly demonstrated that miR-21 plays an important role in AD neurons by moderating their apoptosis upon Aβ exposure [35].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [35]
miR-21 elevation exclusively in SWE cell-transplanted hippocampal cultures may suggest a specific response to SWE cell-induced toxicity.
“Even so, miR-21 elevation exclusively in SWE cell-transplanted hippocampal cultures may suggest a specific response to SWE cell-induced toxicity, as previously described [35].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [35]
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“Earlier studies similarly demonstrated that miR-21 plays an important role in AD neurons by moderating their apoptosis upon Aβ exposure [35].”
Result
- Authors
- Feng, M.-G., Liu, C.-F., Chen, L., Feng, W.-B., Liu, M., Hai, H., & Lu, J.-M.
- Affiliations
- Xianning Central Hospital (CN)
- Second People’s Hospital of Huai’an (CN)
- Corresponding author
- Lu, Jing-Min
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 101
- Pages
- 1003-1007
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2791083334
- Semantic Scholar
- db73f199f8441d9834e62fc85728450100b84a74
- Cited by
- 80
- References
- 39
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 15 · 2023: 8 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- miR-21, Alzheimer's disease, amyloid-beta, PDCD4, PI3K/Akt/GSK-3β signaling, apoptosis, SH-SY5Y cells, Bax/Bcl-2 ratio, neuroprotection, microRNA
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Humans, Signal Transduction, Amyloid beta-Peptides, RNA-Binding Proteins, Apoptosis, MicroRNAs, Cell Line, Tumor, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinase
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