Nafiseh Niknam - Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran.
Shekoofeh.nikooei@gmail.com Nikooei - Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran.
Hassan Ghasemi - Department of Clinical Biochemistry, Abadan School of Medical Sciences, Abadan, Iran.
Seyed Sajjad Zadian - Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Kamran Goudarzi - Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Seyed Majid Ahmadi - Internal Medicine Department of Yasuj Medical School, Yasuj, Iran.
Behnam Alipoor - Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran.

Background: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type ۲ diabetes (T۲D). This study aimed to assess the expression of circulating HOTAIR and uc.۴۸+, examining their correlation with clinical and biochemical variables in T۲D patients, pre-diabetic individuals, and healthy controls. Methods: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in ۶۵ T۲D patients, ۶۳ pre-diabetic individuals, and ۶۳ healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets. Results: Analysis revealed a significantly elevated circulating level of HOTAIR in both T۲D (P < ۰.۰۰۰۱) and pre-diabetic patients (P = ۰.۰۴) compared to controls. ROC analysis demonstrated that, at a cutoff value of ۹.۱, with a sensitivity of ۸۰% and specificity of ۶۲%, HOTAIR could distinguish T۲D patients from controls (AUC = ۰.۷۲۳, ۹۵% CI ۰.۶۳۷-۰.۷۹۹, P < ۰.۰۰۰۱). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA۱c, and insulin resistance (P < ۰.۰۰۵). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.۴۸+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.۴۸+ and systolic blood pressure. Conclusions: This study provides evidence that elevated HOTAIR expression levels are associated with T۲D progression, suggesting their potential as biomarkers for early diagnosis and prognosis.

Diabetes Mellitus, HOTAIR, Long Non-Coding RNA, MicroRNAs.