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Imbalance of TCA-related miRNA-mRNA networks involving IDH2, SDHA, SDHC, and SUCLG1 drives psoriasis development
Lin Chen1, Zhan-Zhong Qiao2, Chang Xu2
1Department of Dermatology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Abstract:
Psoriasis (PsO), a chronic inflammatory skin disorder, is characterized by keratinocyte hyperproliferation and immune dysregulation. Circulating microRNAs (miRNAs) have emerged as potential regulators of systemic metabolic and inflammatory pathways in PsO. In this study, we performed high-throughput sequencing of plasma miRNAs from PsO patients and healthy controls to explore their regulatory roles. Bioinformatic analysis identified several downregulated miRNAs, including hsa-miR-145-5p, hsa-miR-204-5p, hsa-miR-3913-5p, and hsa-miR-10a-5p, which were predicted to target key rate-limiting enzymes of the tricarboxylic acid (TCA) cycle (IDH2, SDHA, SDHC, SUCLG1). A miRNA-mRNA regulatory network was subsequently constructed to illustrate potential interactions between these miRNAs and their target mRNAs. Functional validation using miRNA inhibitors showed significant upregulation of IDH2, SDHA, SDHC, and SUCLG1 mRNA levels compared with the negative control (NC) group. These results suggest that downregulation of miRNAs may relieve the suppression of TCA cycle enzymes, leading to dysregulated glucose metabolism and contributing to the development of psoriasis. In conclusion, this study uncovers a novel mechanism by which miRNA downregulation mediates psoriasis via metabolic regulation and identifies potential targets for combined therapeutic strategies targeting both metabolism and miRNAs. However, the clinical translational relevance of these findings remains insufficiently clarified, and further studies are needed to determine their practical value in diagnosis, severity assessment, and therapeutic intervention.
Insights
Downregulated microRNAs (miRNAs) in psoriasis patients may disrupt glucose metabolism by affecting tricarboxylic acid cycle enzymes. This metabolic dysregulation contributes to psoriasis development, suggesting novel therapeutic targets.
Area of Science:
- Biochemistry
- Immunology
- Genetics
Background:
- Psoriasis (PsO) is a chronic inflammatory skin disease marked by keratinocyte hyperproliferation and immune system imbalance.
- Circulating microRNAs (miRNAs) are increasingly recognized as regulators of metabolic and inflammatory processes in systemic diseases like PsO.
Purpose of the Study:
- To investigate the role of circulating miRNAs in regulating metabolic pathways in psoriasis.
- To identify specific miRNAs and their targets involved in the pathogenesis of psoriasis.
Main Methods:
- High-throughput sequencing of plasma miRNAs from psoriasis patients and healthy controls.
- Bioinformatic analysis to identify differentially expressed miRNAs and predict their mRNA targets.
- Construction of a miRNA-mRNA regulatory network.
- Functional validation using miRNA inhibitors to assess the impact on target gene expression.
Main Results:
- Several miRNAs, including hsa-miR-145-5p, hsa-miR-204-5p, hsa-miR-3913-5p, and hsa-miR-10a-5p, were found to be downregulated in psoriasis patients.
- These downregulated miRNAs were predicted to target key enzymes of the tricarboxylic acid (TCA) cycle (IDH2, SDHA, SDHC, SUCLG1).
- Functional validation confirmed that miRNA inhibition led to significant upregulation of these TCA cycle enzyme mRNAs, suggesting relieved suppression.
Conclusions:
- Downregulation of specific miRNAs may contribute to psoriasis by impairing TCA cycle function and dysregulating glucose metabolism.
- This study reveals a novel mechanism linking miRNA-mediated metabolic regulation to psoriasis pathogenesis.
- Identified miRNA-target interactions offer potential targets for novel therapeutic strategies combining metabolic and miRNA-based interventions, though further clinical validation is required.
