Abstract
OBJECTIVE: This study aimed to assess the expression and clinical significance of hsa-miR-661 in peripheral blood mononuclear cells (PBMCs) of patients with primary Sjögren's syndrome (pSS) and to explore the role of the hsa_circ_0008301/hsa-miR-661/TOLLIP axis in disease progression. METHODS: A total of 58 pSS patients and 58 age- and sex-matched healthy controls, recruited from the General Hospital of Ningxia Medical University between September 2021 and September 2022, were included. Clinical and laboratory data were collected. Hsa-miR-661 expression in PBMCs was measured using quantitative real-time PCR (qRT-PCR). The interaction between hsa_circ_0008301, hsa-miR-661, and TOLLIP was validated using dual-luciferase reporter assays. Group differences were analyzed using t-tests and χ(2) tests. Correlations with clinical and laboratory parameters were examined using Spearman correlation and logistic regression. Diagnostic utility was evaluated via receiver operating characteristic (ROC) curve analysis, with P < 0.05 considered statistically significant. RESULTS: Hsa-miR-661 expression was significantly upregulated in pSS patients compared to controls. Increased levels were associated with longer disease duration, lower C3 and platelet counts, higher ESR, more severe xerostomia, and elevated ESSDAI scores. ROC analysis demonstrated that hsa-miR-661 effectively distinguished pSS patients from healthy individuals and discriminated between high- and low-activity disease states. Functional assays confirmed that hsa_circ_0008301 directly interacts with hsa-miR-661, which targets and regulates TOLLIP. CONCLUSION: Hsa-miR-661 is markedly elevated in pSS and closely correlates with disease activity and key clinical indicators. These findings suggest its potential as a diagnostic biomarker and therapeutic target in pSS. Key Points • Hsa-miR-661 is markedly upregulated in peripheral blood mononuclear cells of pSS patients and is closely associated with clinical manifestations and disease activity. • It demonstrates strong diagnostic accuracy (AUC = 0.892) and effectively distinguishes between high and low disease activity (AUC = 0.779). • The circRNA_0008301/miR-661/TOLLIP axis provides mechanistic insight into pSS pathogenesis and highlights a potential therapeutic target.