Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women.

Abstract

An increasing risk of developing osteoporosis which is characterized by bone production weakness and microarchitectural deterioration is found among postmenopausal women. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues in response to local disease severity including bone diseases. Herein, we set out to identify candidate miRNAs predictable for osteoporosis incidence in postmenopausal elderly women. The circulating miRNA expression profiles deposited in the dataset accessioned as GSE201543 were downloaded from the GEO database. The study included 176 postmenopausal women who underwent BMD testing, including 96 women reporting osteoporosis and 70 women reporting normal BMD. All subjects were submitted their serum samples for measurements of bone metabolism markers. The miRNA expression profiles of the GSE201543 dataset were differentially analyzed and found 97 miRNAs being upregulated concomitantly with 31 miRNAs being downregulated in the serum samples between osteoporotic postmenopausal women and postmenopausal women with normal BMD. Osteoporotic postmenopausal women were demonstrated with elevated serum levels of miR-340-5p and miR-506-3p when compared to normal postmenopausal women. Pearson correlation analysis demonstrated that circulating miR-340-5p and miR-506-3p expressions were increased as BAP, β-CTx, and PINP levels increased, but osteocalcin and 25-(OH)VitD levels are declined in osteoporotic postmenopausal women. Results of the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) showed circulating miR-340-5p and miR-506-3p expressions alone or combined together produced 0.843 AUC, 0.851 AUC, and 0.935 AUC, respectively, when used to predict the incidence of osteoporosis in postmenopausal women. Our work suggested that circulating miR-340-5p and miR-506-3p function as osteo-miRNAs in postmenopausal women and may serve as potential noninvasive biomarkers for the incidence of osteoporosis in postmenopausal women.