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Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus

  • Authors:
    • Mengxue Liu
    • Hong Qiao
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Endocrinology and Metabolism, The Second Affliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 158
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    Published online on: April 10, 2025
       https://doi.org/10.3892/mmr.2025.13523
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Abstract

The present study aimed to elucidate the roles and mechanisms of gene biomarkers associated with mitochondrial dysfunction in the progression of Type 2 diabetes mellitus (T2DM). It conducted an analysis of differentially expressed genes related to mitochondrial dysfunction in T2DM and employed bioinformatics approaches to predict potential target drugs for key biomarkers. Additionally, the present study used the EPIC algorithm to examine immune cell infiltration in T2DM. Furthermore, the single‑cell RNA sequencing dataset GSE221156 was analyzed to identify specific cell types involved in T2DM. The expression of biomarkers was investigated through cellular experiments to assess the effect of marker genes on macrophage polarization. A total of five biomarker genes associated with T2DM were identified, namely ERAP2, HLA‑DQB1, HLA‑DRB5, MAP1B and OAS3. The combined detection of these genes yielded a risk‑predictive area under the curve value of 0.833 for T2DM. These five marker genes may serve as potential targets for valproic acid (VPA). During the progression of T2DM, there is an increase in macrophage numbers, with these genes being highly expressed in macrophages. In a high glucose‑induced RAW264.7 macrophage model, the expressions of MAP1B and OAS3 were upregulated. Notably, the knockdown of OAS3 markedly reduced M1 macrophage polarization, indicating OAS3 facilitates M1 macrophage polarization in a high‑glucose environment. The downregulation of OAS3 expression attenuated M1 macrophage polarization by inhibiting mTORC activation. In conclusion, five candidate biomarkers for T2DM were identified that may serve as therapeutic targets for VPA and are associated with immune infiltration in T2DM. Among these, OAS3 enhances M1 macrophage polarization in a high‑glucose environment by regulating the mTORC1 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Liu M and Qiao H: Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus. Mol Med Rep 31: 158, 2025.
APA
Liu, M., & Qiao, H. (2025). Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus. Molecular Medicine Reports, 31, 158. https://doi.org/10.3892/mmr.2025.13523
MLA
Liu, M., Qiao, H."Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus". Molecular Medicine Reports 31.6 (2025): 158.
Chicago
Liu, M., Qiao, H."Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus". Molecular Medicine Reports 31, no. 6 (2025): 158. https://doi.org/10.3892/mmr.2025.13523
Copy and paste a formatted citation
x
Spandidos Publications style
Liu M and Qiao H: Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus. Mol Med Rep 31: 158, 2025.
APA
Liu, M., & Qiao, H. (2025). Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus. Molecular Medicine Reports, 31, 158. https://doi.org/10.3892/mmr.2025.13523
MLA
Liu, M., Qiao, H."Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus". Molecular Medicine Reports 31.6 (2025): 158.
Chicago
Liu, M., Qiao, H."Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus". Molecular Medicine Reports 31, no. 6 (2025): 158. https://doi.org/10.3892/mmr.2025.13523
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