Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China.
Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, 410011 Hunan, China.
Mediators Inflamm. 2021 May 4;2021:5566453. doi: 10.1155/2021/5566453. eCollection 2021.
During the initial stage of type 1 diabetes, prolonged exposure of pancreatic -cell to proinflammatory cytokines such as IL-1, TNF-, and IFN- results in a decreased capacity to produce and release insulin, as well as cell loss by apoptosis. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs (ncRNAs) with closed loop with no free ends. circRNAs have been reported to be participated in the development of many diseases. As little is known about their role in insulin-secreting cells, this study is aimed at evaluating their contribution in the process of inflammation-induced -cell damage.
circRNA expression profile of MIN6 cells stimulated with a mix of cytokines, including IL-1, IFN-, and TNF-, was detected by circRNA microarrays. Four dysregulated circRNAs were validated by qRT-PCR. The involvement of the selected circRNAs in -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.
1020 upregulated and 902 downregulated circRNAs were identified in cytokines-treated -cells. Inhibition of circRNAs 000286 and 017277 in -cells could promote -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- and MAPK signaling pathways.
The data shows that circRNAs may be involved in proinflammatory cytokines-mediated -cell dysfunction and suggests the involvement of circRNAs in the development of type 1 diabetes.
在 1 型糖尿病的初始阶段，胰岛细胞长时间暴露于促炎细胞因子（如 IL-1、TNF-和 IFN-）会导致胰岛素产生和分泌能力下降，并通过细胞凋亡导致细胞丢失。环状 RNA（circRNA）是一类新的内源性非编码 RNA（ncRNA），具有无游离末端的闭合环。已经有报道称 circRNA 参与了许多疾病的发生。由于对其在胰岛素分泌细胞中的作用知之甚少，本研究旨在评估其在炎症诱导的β细胞损伤过程中的作用。
通过 circRNA 微阵列检测经细胞因子（包括 IL-1、IFN-和 TNF-）刺激的 MIN6 细胞的 circRNA 表达谱。通过 qRT-PCR 验证了 4 个上调的 circRNA。在 MIN6 细胞中抑制这些 circRNA 后，检测它们在β细胞功能障碍中的作用。使用 microRNA 靶基因预测软件和多种生物信息学方法预测 circRNA 的靶基因，并分析 circRNA 的可能功能。
在细胞因子处理的β细胞中，鉴定出 1020 个上调和 902 个下调的 circRNA。在β细胞中抑制 circRNA 000286 和 017277 可促进β细胞凋亡，并影响胰岛素的生物合成和分泌。GO 分析富集了转录调控和基因表达调控等术语，KEGG 分析富集了 TGF-β和 MAPK 信号通路等主要通路。
数据表明 circRNA 可能参与促炎细胞因子介导的β细胞功能障碍，并提示 circRNA 参与 1 型糖尿病的发生。
