Assessing the Role of lncRNA GAS5 in Thyroid Function Regulation and Their Potential Use as Biomarkers for Hyperthyroidism Management

<ns5:p> Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators of cellular processes, including those implicated in autoimmune and endocrine disorders. However, their role in thyroid function, particularly hyperthyroidism, remains insufficiently defined. Growth Arrest-Specific 5 (GAS5) is a lncRNA with established functions in tumor suppression, cell cycle arrest, and apoptosis, and may therefore influence thyroid cell regulation and hormone production. This study aimed to assess the expression of GAS5 in patients with hyperthyroidism and evaluate its potential utility as a biomarker. Thirty whole-blood samples from hyperthyroid patients and 20 samples from healthy controls were analyzed. Total RNA was extracted using Trizol, and complementary DNA (CDNA) was synthesized with oligo(dT) primers. GAS5 expression was quantified by qRT-PCR, and statistical analysis was performed using One-Way ANOVA, correlation testing, and visualization in R. GAS5 expression was significantly decreased in hyperthyroid patients compared with controls (mean 0.429 vs. 1.004, <ns5:italic>p</ns5:italic> < 0.0001), with non-overlapping confidence intervals. Approximately 77% of patient samples showed expression levels below one. Pairwise comparisons confirmed highly significant differences between groups ( <ns5:italic>p</ns5:italic> = 0.0001). Spearman correlation revealed an inverse relationship between GAS5 and T3 ( <ns5:italic>r</ns5:italic> = –0.454, <ns5:italic>p</ns5:italic> = 0.001) as well as T4 ( <ns5:italic>r</ns5:italic> = –0.438, <ns5:italic>p</ns5:italic> = 0.001). The AUC of T4 was 0.993 (95% confidence interval: 0.981–1.000), TSH 0.967 (0.901–0.995) and T3 0.963 (0.898–0.992), indicating the good diagnostic performance of traditional thyroid hormones. These findings indicate that GAS5 downregulation is associated with increased thyroid hormone production, suggesting a potential regulatory role in hyperthyroidism. GAS5 expression could therefore represent a promising early biomarker for individuals at risk of thyroid dysfunction. </ns5:p>