Involvement of circRNAs in Proinflammatory Cytokines-Mediated β-Cell Dysfunction

circRNA 参与促炎细胞因子介导的 β 细胞功能障碍

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作者:Zhen Wang, Chao Deng, Ying Zheng

Aim

During the initial stage of type 1 diabetes, prolonged exposure of pancreatic β-cell to proinflammatory cytokines such as IL-1β, TNF-α, and IFN-γ

Conclusions

The data shows that circRNAs may be involved in proinflammatory cytokines-mediated β-cell dysfunction and suggests the involvement of circRNAs in the development of type 1 diabetes.

Methods

circRNA expression profile of MIN6 cells stimulated with a mix of cytokines, including IL-1β, IFN-γ, and TNF-α, was detected by circRNA microarrays. Four dysregulated circRNAs were validated by qRT-PCR. The involvement of the selected circRNAs in β-cell dysfunction was tested after their inhibition in MIN6 cells. MicroRNA target prediction software and multiple bioinformatic approaches were used to predict the targeting genes of circRNAs and analyze possible functions of the circRNAs.

Results

1020 upregulated and 902 downregulated circRNAs were identified in cytokines-treated β-cells. Inhibition of circRNAs 000286 and 017277 in β-cells could promote β-cell apoptosis and affect insulin biosynthesis and secretion. GO analysis enriched terms such as regulation of transcription and regulation of gene expression and KEGG analysis enriched top pathways included TGF-β and MAPK signaling pathways. Conclusions: The data shows that circRNAs may be involved in proinflammatory cytokines-mediated β-cell dysfunction and suggests the involvement of circRNAs in the development of type 1 diabetes.

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