Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China.
Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
Front Endocrinol (Lausanne). 2022 Jan 18;12:790591. doi: 10.3389/fendo.2021.790591. eCollection 2021.
Chronic stress plays an important role in the development of type 2 diabetes (T2D). Circular RNAs (circRNAs) play significant roles in regulating the pathogenesis of diseases by regulating gene expression. The aim of the present study was to identify the association between hsa_circ_0111707 and stress-related T2D.
The present study was performed based on a three-part design. The association between hsa_circ_0111707 in peripheral blood mononuclear cells (PBMCs) and T2D and stress-related variables were assessed in a cross-sectional study. The causal relationship of hsa_circ_0111707 on T2D was further investigated in a nested case-control study. miR-144-3p as the miRNA target of hsa_circ_0111707 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
The relative expression of hsa_circ_0111707 was significantly lower in the T2D and impaired fasting glucose (IFG) cases in comparison with controls. The hsa_circ_0111707 expression was significantly negatively correlated with miR-144-3p expression and plasma cortisol concentration and positively correlated with expression. In addition, hsa_circ_0111707 expression was negatively correlated with scores of "demands at work" and "insecurity at work" of Copenhagen Psychosocial Questionnaire (COPSOQ). Decreased hsa_circ_0111707 expression was associated with increased risk of T2D development. Functional analysis demonstrated that hsa_circ_0111707 functions as a sponge for miR-144-3p.
hsa_circ_0111707 is associated with risk of T2D development sponging miR-144-3p. hsa_circ_0111707 in PBMCs can be considered a potential biomarker of stress-related T2D.
慢性应激在 2 型糖尿病（T2D）的发展中起着重要作用。环状 RNA（circRNA）通过调节基因表达在调节疾病发病机制方面发挥着重要作用。本研究旨在确定 hsa_circ_0111707 与应激相关的 T2D 之间的关联。
本研究基于三部分设计进行。在横断面研究中，评估了外周血单个核细胞（PBMC）中 hsa_circ_0111707 与 T2D 和应激相关变量之间的关联。在巢式病例对照研究中进一步研究了 hsa_circ_0111707 对 T2D 的因果关系。通过双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）实验验证了 hsa_circ_0111707 的 miRNA 靶标 miR-144-3p。
与对照组相比，T2D 和空腹血糖受损（IFG）病例中 hsa_circ_0111707 的相对表达水平显著降低。hsa_circ_0111707 的表达与 miR-144-3p 的表达呈显著负相关，与皮质醇浓度呈显著正相关，与 呈显著负相关。此外，hsa_circ_0111707 的表达与哥本哈根心理社会问卷（COPSOQ）的“工作需求”和“工作不安全”评分呈显著负相关。hsa_circ_0111707 表达降低与 T2D 发病风险增加相关。功能分析表明，hsa_circ_0111707 作为 miR-144-3p 的海绵发挥作用。
hsa_circ_0111707 与 T2D 发病风险相关，通过海绵作用于 miR-144-3p。PBMC 中的 hsa_circ_0111707 可被视为应激相关 T2D 的潜在生物标志物。
