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Cited by 11Parkinson's Disease Mechanisms and TreatmentsMicroRNA in disease regulationNuclear Receptors and Signaling

MiRNA-1976 Regulates the Apoptosis of Dopaminergic Neurons by Targeting the PINK1 Gene

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Qiu, Feng, Wu, Yue, Xie, Guojin, Cao, Hui, Du, Mingyang, Jiang, Haibo·2023·Journal of Integrative Neuroscience
DOI 10.31083/j.jin2202045
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Abstract

Introduction: Parkinson’s disease (PD), which is a neurodegenerative disease, requires urgently needed biomarkers to explore its mechanism. We screened for differences in the expression of microRNAs (miRNAs) and identified miR-1976 as a possible biomarker. Methods: Twenty-three patients and 30 controls were included in this study. Dopaminergic neurons from C57/BL mice were cultured. The miRNA expression profiles were analyzed using an miRNA microarray. MiR-1976 was identified as an miRNA that was differentially expressed between PD patients and age-matched controls. Lentiviral vectors were constructed, then apoptosis in dopaminergic neurons was analyzed using MTS (multicellular tumor spheroids) and flow cytometry. Transfection of miR-1976 mimics into MES23.5 cells was performed, and target genes and biological effects were analyzed. Results: Overexpression of miR-1976 increased apoptosis and mitochondrial damage in dopaminergic neurons. PINK1 (PINK1-induced kinase 1) was the most common target protein of miR-1976, and silencing of PINK1 caused mitochondrial damage and increased apoptosis of MES23.5 cells. Conclusions: MiR-1976 is a newly discovered miRNA that exhibits a high degree of differential expression with respect to the apoptosis of dopaminergic neurons. Given these results, increased expression of miR-1976 may increase the risk of PD by targeting PINK1 and may therefore be a useful biomarker for PD.

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  • Of the five miRNAs experimentally confirmed to directly target PINK1, only miR-27b was among the top hits in the genome-wide screen.

    “However, of the five miRNAs that have been experimentally confirmed to directly target PINK1 [37–39], only miR-27b [32] was among the top hits in our genome-wide screen.”

    From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [38]

    Section 3.3 reports a luciferase assay showing that miR-1976 directly binds the PINK1 3′-UTR, supporting its inclusion among experimentally confirmed PINK1-targeting miRNAs. This paper does not establish that there are five such miRNAs in total. The genome-wide-screen finding is separately attributed to citation [32], not this source. (LLM, conf=0.86)

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Authors
Qiu, F., Wu, Y., Xie, G., Cao, H., Du, M., & Jiang, H.
Affiliations
  • Nanjing Brain Hospital (CN)
  • Second Affiliated Hospital of Nanjing Medical University (CN)
  • Nanjing Children's Hospital (CN)
Corresponding author
Qiu, Feng
ORCID
Venue
Journal of Integrative Neuroscience
Publisher
IMR Press
Published
2023-02-22
Volume
22
Issue
2
Pages
45-45
ISSN
  • 0219-6352 (ISSN-L)
  • 1757-448X
DOI
10.31083/j.jin2202045
OpenAlex
W4322183398
Cited by
11
References
26
Citations by year
2026: 1 · 2025: 2 · 2024: 6 · 2023: 2
FWCI
1.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Integrative Neuroscience (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Nanjing Medical Science and technique Development Foundation (QRX17086)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
PINK1, Parkinson's disease, dopaminergic neurons, neuronal apoptosis, mitochondrial damage, microRNA biomarkers, miRNA expression profiling, MES23.5 cells
MeSH terms
PTEN-Induced Putative Kinase, Animals, Mice, Inbred C57BL, Parkinson Disease, Protein Kinases, Apoptosis, Neurodegenerative Diseases, MicroRNAs, Mice, Dopaminergic Neurons

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