Imbalance of TCA-related miRNA-mRNA networks involving IDH2, SDHA, SDHC, and SUCLG1 drives psoriasis development.

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.