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. 2025 May 2.
doi: 10.1007/s10528-025-11116-0. Online ahead of print.

Dysregulated Long Non-coding RNAs SNHG15 and OTUD6B-AS1 in Systemic Lupus Erythematosus: Insights from Bioinformatics Analysis and Experimental Validation

Ahmad Golestanifar  1   2 , Arezo Masroor  3 , Hengameh Khedri  2 , Shiva Zeini  4 , Azim Nejatizadeh  5
Affiliations

Dysregulated Long Non-coding RNAs SNHG15 and OTUD6B-AS1 in Systemic Lupus Erythematosus: Insights from Bioinformatics Analysis and Experimental Validation

Ahmad Golestanifar et al. Biochem Genet. .

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation and multi-organ involvement. This study focuses on the dysregulated expression of lncRNAs SNHG15 and OTUD6B-AS1 as potential biomarkers for disease progression and diagnostics. A comprehensive bioinformatics analysis of RNA-sequencing data from PBMCs of SLE patients and healthy controls identified differentially expressed lncRNAs, miRNAs, and mRNAs. The DAVID tool was employed for functional enrichment analyses to elucidate the biological pathways and functions associated with these differentially expressed genes. Concurrently, the STRING database was used to predict protein-protein interactions, enhancing our understanding of the molecular interactions and networks involved. Additionally, the relationships between lncRNAs, miRNAs, and mRNAs were explored through the construction of a competing endogenous RNA (ceRNA) network, visualized using Cytoscape. The findings from the bioinformatics analysis were substantiated by qPCR, which validated the differential expression of the lncRNAs SNHG15 and OTUD6B-AS1 in a larger cohort of samples, affirming their potential roles as biomarkers for SLE. The findings revealed significant up-regulation of SNHG15 (fold change = 2.01, p = 0.0011) and down-regulation of OTUD6B-AS1 (fold change = 0.26, p < 0.0001) in SLE patients compared to controls. Correlation analyses linked OTUD6B-AS1 expression with hematological and inflammatory markers, while SNHG15 was associated with liver function indicators. ROC analysis demonstrated high diagnostic accuracy for both lncRNAs, particularly OTUD6B-AS1. This study establishes SNHG15 and OTUD6B-AS1 as promising biomarkers for SLE, highlighting their distinct associations with immune and organ-specific pathology. The robust diagnostic performance of OTUD6B-AS1, evidenced by its high sensitivity and specificity, suggests its utility in developing more accurate diagnostic tests for SLE. Furthermore, the correlation of these lncRNAs with disease activity markers underscores their potential role in monitoring disease progression and severity in SLE patients.

Keywords: Bioinformatics analysis; LINC00963; OTUD6B-AS1; RNA-seq; SNHG15; Systemic lupus erythematosus; lncRNA–miRNA–mRNA.

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Conflict of interest statement

Declarations. Competing interests: The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest. Ethical Approval: The study involving human participants was reviewed and approved by the Ethics Committee of the Hormozgan University of Medical Sciences of Bandar Abbas City (Approval Number: IR.HUMS.REC.1402.370). Consent to Participate: The patients/participants provided written informed consent to participate in this study. Consent to Publish: Not applicable.

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