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Basic Research
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N6-Methyladenosine Methyltransferase METTL3 Alleviates Diabetes-Induced Testicular Damage through Modulating TUG1/Clusterin Axis
Yuan Tian, Yue-Hai Xiao, Chao Sun, Bei Liu, Fa Sun
Diabetes Metab J. 2023;47(2):287-300.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0306
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AbstractAbstract PDFPubReader   ePub   
Background
The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage.
Methods
In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury.
Results
METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells.
Conclusion
This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

Citations

Citations to this article as recorded by  
  • Negative Regulation of LINC01013 by METTL3 and YTHDF2 Enhances the Osteogenic Differentiation of Senescent Pre‐Osteoblast Cells Induced by Hydrogen Peroxide
    Jiaxin Song, Yuejun Wang, Zhao Zhu, Wanqing Wang, Haoqing Yang, Zhaochen Shan
    Advanced Biology.2024;[Epub]     CrossRef
  • Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1
    Mohammed Ageeli Hakami
    Saudi Journal of Biological Sciences.2024; 31(5): 103976.     CrossRef

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