Emerging role of hsa_circ_0000652, hsa-miR-21, SMAD2, and Foxo1 in type 2 diabetes mellitus pathogenesis

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene Pub Date : 2025-02-01 DOI:10.1016/j.humgen.2025.201386

Abeer Mostafa , Azza Abusree Ahmed , Radwa T.M. Hassanien , Hala Mahfouz , Marwa Salah , Heba M. Amr , Sally A. Fahim

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引用次数: 0

Abstract

Background

Diabetes mellitus (DM) is considered a metabolic disorder widely distributed worldwide. Optimal options of treatment and their related mechanisms are still unclear despite intense investigations. MicroRNAs (miRNAs) are small noncoding that control molecular signaling pathways in various diseases including DM. miR-21 has a role in multiple biological processes as apoptosis, and proliferation of the cell. The aim of the present work is to investigate the epigenetic control of DM pathogenesis.

Methods

The current study enrolled 30 healthy controls and 30 patients diagnosed with type II diabetes (T2DM). miR-21, hsa_circ_0000652, Foxo1, and SMAD2 expressions were evaluated by qRT-PCR. Moreover, Bioinformatics analysis of hsa_circ_0000652 and its targeted pathways was investigated.

Results

hsa_circ_0000652 and miR-21 were up-regulated in T2DM. hsa_circ_0000652 restricts the inhibitory effect of miR-21 of its targeted genes (SMAD2, Foxo1) that were up regulated in diabetic patients (P value <0.001), miR-21 was significantly correlated with hsa_circ_0000652, SMAD2, and Foxo1 (p-values = 0.022, 0.003, and < 0.001, respectively). ROC analysis of hsa-miR-21 and hsa_circ_0000652 revealed that they are significant diagnostic factors for T2DM (P value <0.001, AUC =0.98, 0.927), they also represent a significant risk factor for occurrence of T2DM.

Conclusion

hsa-miR-21 and hsa_circ_0000652 are potent regulators in DM pathogenesis and could be novel therapeutic targets for treatment and prevention of DM.

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hsa_circ_0000652、hsa-miR-21、SMAD2和Foxo1在2型糖尿病发病机制中的新作用

糖尿病（DM）是一种广泛分布于世界各地的代谢疾病。尽管进行了大量的研究，但最佳治疗方案及其相关机制仍不清楚。MicroRNAs （miRNAs）是控制包括dm在内的多种疾病的分子信号通路的小非编码分子。miR-21在细胞凋亡和细胞增殖等多种生物学过程中发挥作用。本研究的目的是探讨糖尿病发病机制的表观遗传控制。方法本研究纳入30名健康对照和30名诊断为II型糖尿病（T2DM）的患者。qRT-PCR检测miR-21、hsa_circ_0000652、Foxo1和SMAD2的表达。此外，我们还对hsa_circ_0000652及其靶向通路进行了生物信息学分析。结果T2DM患者中shsa_circ_0000652和miR-21表达上调。hsa_circ_0000652限制了miR-21对其在糖尿病患者中上调的靶基因（SMAD2、Foxo1）的抑制作用（P值<；0.001）， miR-21与hsa_circ_0000652、SMAD2、Foxo1显著相关(P值= 0.022、0.003、<；分别为0.001)。对hsa-miR-21和hsa_circ_0000652的ROC分析显示，它们是T2DM的重要诊断因素（P值<；0.001, AUC =0.98, 0.927），也是T2DM发生的重要危险因素。结论hsa- mir -21和hsa_circ_0000652在糖尿病发病过程中具有重要调控作用，可能成为治疗和预防糖尿病的新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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