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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1445033
This article is part of the Research Topic High-throughput Sequencing-based Investigation of Chronic Disease Markers and Mechanisms, Volume II View all 8 articles

Bioinformatical analysis and experimental validation of endoplasmic reticulum stress-related biomarker genes in type 2 diabetes mellitus

Provisionally accepted
Lili Yao Lili Yao 1Jie Xu Jie Xu 2Xu Zhang Xu Zhang 3Yuqing Chen Yuqing Chen 1Xiaoyu Liu Xiaoyu Liu 2Xuchu Duan Xuchu Duan 2*
  • 1 Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • 2 Nantong University, Nantong, Jiangsu Province, China
  • 3 Wuxi No.2 People's Hospital, Nanjing Medical University, Wuxi, China

The final, formatted version of the article will be published soon.

    Endoplasmic reticulum stress (ERS) is a prominent etiological factor in the pathogenesis of diabetes. Nevertheless, the mechanisms through which ERS contributes to the development of diabetes remain elusive. This study aimed to identify ERS-related biomarker genes in type 2 diabetes mellitus (T2DM). By analyzing the transcriptional expression profiles of the GEO datasets, 49 T2DMrelated differentially expressed genes (DEGs) were screened out in diabetic islets.After the intersection with ERS-related genes, RTN1, CLGN, PCSK1, IAPP, ILF2, IMPA1, CCDC47, and PTGES3 were identified as ERS-related DEGs in T2DM, which were revealed to be involved in protein folding, membrane composition, and metabolism regulation. Receiver operating characteristic (ROC) and Least Absolute Shrinkage and Selection Operator (LASSO) analysis further screened out CLGN, ILF2, and IMPA1 as biomarker genes with high value and reliability for diagnostic purposes. These three genes were then demonstrated to be targeted by the transcription factors and miRNAs, including CEBPA, CEBPB, miR-197-5p, miR-6133, and others. Among these miRNAs, the expression of miR-197-5p, miR-320c, miR-1296-3P and miR-6133 was down-regulated, while that of miR-4462, miR-4476-5P and miR-7851-3P was up-regulated in diabetic samples. Small molecular drugs, including D002994, D001564, and others, were predicted to target these genes potentially. qPCR and Elisa analysis both validated the same expression alteration of the ERS-related biomarker genes in diabetic mice and T2DM patients. These findings will offer innovative perspectives for clinical diagnosis and treatment strategies for T2DM.

    Keywords: type 2 diabetes mellitus, Biomarker gene, Endoplasmic Reticulum Stress, Bioinformatical analysis, experimental validation, diagnosis

    Received: 06 Jun 2024; Accepted: 18 Oct 2024.

    Copyright: © 2024 Yao, Xu, Zhang, Chen, Liu and Duan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xuchu Duan, Nantong University, Nantong, 226019, Jiangsu Province, China

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