A functional polymorphism at the miR-25-3p binding site in the 3′-untranslated region of the S1PR1 gene decreases the risk of osteoporosis in Chinese postmenopausal women

Abstract

The low bone mineral density due to abnormally activated osteoclasts can induce bone disorders such as osteopenia and osteoporosis. MiR-25-3p modulates sphingosine-1-phosphate receptor 1 (S1PR1) expression to enhance osteoclast motivation. The association between miR-25 rs41274221 polymorphism and osteoporosis susceptibility is unknown. Herein, 300 patients with osteoporosis and 320 healthy controls were genotyped using polymerase chain reaction and Sanger sequencing to explore the role of miR-25 rs41274221 polymorphism in osteoporosis. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression analysis. Additionally, this study also investigated the effect of miR-25 rs41274221 polymorphism on the expression of miR-25 and its target gene S1PR1 through luciferase reporter gene, qRT-PCR, and Western blot. The rs41274221 in miR-25 was found to be positively associated with osteoporosis and can be viewed as a protective factor. Furthermore, miR-25 rs41274221 polymorphism decreased the risk of osteoporosis among smokers. The TargetScan database predictions and dual-luciferase activity demonstrated that S1PR1 may be the target gene of miR-25. MiR-25 downregulated the S1PR1 mRNA and protein expressions. Patients with the AA genotype of rs41274221 polymorphism showed higher S1PR1 expression compared with the GG genotype. In conclusion, miR-25 rs41274221 polymorphism decreases the risk of osteoporosis through modifying the binding with S1PR1 and may serve as a novel biomarker for early diagnosis of osteoporosis.