The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.
Ningbo University School of Medicine, Ningbo, China.
J Clin Lab Anal. 2022 Aug;36(8):e24583. doi: 10.1002/jcla.24583. Epub 2022 Jul 2.
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease closely related to obesity, a growing global health problem. T2DM is characterized by decreased islet beta-cell mass and impaired insulin release from these cells, and this dysfunction is exacerbated by hyperglycemia (glucolipotoxicity). Circular RNAs (circRNAs) are abnormally expressed and play a regulatory role in T2DM.
This study aimed to evaluate the function and molecular mechanism of hsa_circ_0115355 in the progression of T2DM.
The regulatory effect of hsa_circ_0115355 on INS-1 cell function was assessed under glucolipotoxicity by MTT, flow cytometry analysis, and insulin secretion assay. Dual-luciferase experiments revealed a direct interaction of hsa_circ_0115355 with miR-145 and miR-145 with SIRT1. Furthermore, the regulatory role of the hsa_circ_0115355/miR-145/SIRT1 axis was verified by examining the function of INS-1.
In this study, hsa_circ_0115355 was significantly underexpressed in both patients with T2DM and INS-1 cell lines. This study thus showed that hsa_circ_0115355 inhibits the occurrence and development of T2DM by regulating the expression of SIRT1 by adsorbing miR-145.
The underexpression hsa_circ_0115355 is also a potential novel diagnostic marker and therapeutic target for T2DM.
2 型糖尿病（T2DM）是一种与肥胖密切相关的复杂代谢性疾病，是一个日益严重的全球性健康问题。T2DM 的特征是胰岛β细胞数量减少和这些细胞胰岛素释放受损，这种功能障碍因高血糖（糖脂毒性）而加剧。环状 RNA（circRNA）表达异常，在 T2DM 中发挥调节作用。
本研究旨在评估 hsa_circ_0115355 在 T2DM 进展中的功能和分子机制。
通过 MTT、流式细胞术分析和胰岛素分泌测定评估 hsa_circ_0115355 在糖脂毒性下对 INS-1 细胞功能的调节作用。双荧光素酶实验显示 hsa_circ_0115355 与 miR-145 直接相互作用，miR-145 与 SIRT1 相互作用。此外，通过检查 INS-1 的功能，验证了 hsa_circ_0115355/miR-145/SIRT1 轴的调节作用。
在这项研究中，hsa_circ_0115355 在 T2DM 患者和 INS-1 细胞系中均明显低表达。因此，本研究表明，hsa_circ_0115355 通过吸附 miR-145 调节 SIRT1 的表达来抑制 T2DM 的发生和发展。
hsa_circ_0115355 的低表达也是 T2DM 的一个潜在的新型诊断标志物和治疗靶点。
