Integrative analysis of DEGs and regulatory networks in T2DM: identification of core genes and regulatory elements as novel therapeutic targets.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI:10.1007/s13205-025-04453-9

Madhu Yadav, Yusuf Akhter

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引用次数: 0

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic and debilitating condition characterized by both insufficient production of insulin and insulin resistance, leading to poor blood sugar control. India ranks second globally in diabetes prevalence, with approximately 77 million individuals currently affected by the disease. Although extensive research has been conducted, the molecular mechanisms of T2DM remain inadequately understood, which continues to pose challenges in the development of effective therapeutic strategies. In this study, we analyzed the GSE25724 microarray dataset and identified 2048 differentially expressed genes (DEGs) associated with T2DM. Among these, key hub genes include ESR1, JUN, STAT3, CALM3, FN1, CXCL8, HIF-1α, FOXO3, CASP3, APP, and HSPA8, which were identified through Cytoscape as central regulators, implicating inflammatory and immune pathways in T2DM progression. Using NetworkAnalyst, identified key transcription factors (DDIT3, KLF12, HINF, SLC17A6, SP1, MAP1B, TUSC3 and GALNT1) and microRNA (hsa-miR-16-5p, hsa-miR-26b-5p, hsa-miR-93-5p, hsa-miR-192-5p, and hsa-miR-155-5p) that regulates important genes involved in T2DM, highlighting the complex gene regulation behind the disease. Genes such as MAPK1, JUN, and CREB1 from key signalling pathways, as well as PCSK1, COL3A1, and PTGS2 identified through gene-disease association databases, have strong links to type 2 diabetes. These genes are believed to play potential roles in the development and progression of T2DM by participating in biological pathways relevant to the disease. Among the hub genes, POU3F1, CX3CL1, and PCSK1 exhibited strong diagnostic accuracy for T2DM, with each achieving ROC curve and AUC values greater than 0.90. This indicates exceptional sensitivity and specificity in distinguishing T2DM from non-diabetic controls. Overall, our findings shed light on the molecular mechanism of T2DM and identify novel biomarkers and therapeutic targets that may support future precision medicine strategies to enhance diagnosis and treatment outcomes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04453-9.

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T2DM中deg和调控网络的综合分析：鉴定核心基因和调控元件作为新的治疗靶点。

2型糖尿病（T2DM）是一种慢性衰弱疾病，其特征是胰岛素分泌不足和胰岛素抵抗，导致血糖控制不良。印度的糖尿病患病率在全球排名第二，目前约有7700万人患有糖尿病。尽管已经进行了广泛的研究，但T2DM的分子机制仍未得到充分的了解，这继续给制定有效的治疗策略带来挑战。在这项研究中，我们分析了GSE25724微阵列数据集，并确定了2048个与T2DM相关的差异表达基因（deg）。其中，关键枢纽基因包括ESR1、JUN、STAT3、CALM3、FN1、CXCL8、HIF-1α、FOXO3、CASP3、APP和HSPA8，这些基因通过Cytoscape被鉴定为中枢调节因子，参与T2DM进展中的炎症和免疫途径。使用NetworkAnalyst，确定了关键转录因子（DDIT3, KLF12， HINF, SLC17A6, SP1, MAP1B， TUSC3和GALNT1）和microRNA (hsa-miR-16-5p, hsa-miR-26b-5p, hsa-miR-93-5p， hsa-miR-192-5p和hsa-miR-155-5p)，这些转录因子调节了T2DM相关的重要基因，突出了该疾病背后复杂的基因调控。来自关键信号通路的基因，如MAPK1、JUN和CREB1，以及通过基因疾病关联数据库发现的PCSK1、COL3A1和PTGS2，与2型糖尿病有很强的联系。这些基因被认为通过参与与该疾病相关的生物学途径，在T2DM的发生和进展中发挥潜在作用。中心基因中，POU3F1、CX3CL1和PCSK1对T2DM的诊断准确性较强，其ROC曲线和AUC值均大于0.90。这表明在区分T2DM与非糖尿病对照中具有特殊的敏感性和特异性。总的来说，我们的研究结果揭示了T2DM的分子机制，并确定了新的生物标志物和治疗靶点，这可能支持未来的精准医学策略，以提高诊断和治疗效果。补充信息：在线版本包含补充资料，下载地址：10.1007/s13205-025-04453-9。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.