Dataset Information

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

ABSTRACT:

Background

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.

Methodology/principal findings

We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression.

Conclusions/significance

Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.

SUBMITTER: Cao Z

PROVIDER: S-EPMC4018259 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

Cao Zheng Z Moore Benjamin T BT Wang Yang Y Peng Xian-Hao XH Lappe Joan M JM Recker Robert R RR Xiao Peng P

PloS one 20140512 5

<h4>Background</h4>MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating ...[more]

PMID: 24820117

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Project description:BackgroundMany researchers focused on diverse miRNAs in the progression of osteoporosis in postmenopausal women. This study aimed to evaluate the association between plasma miRNA-21-5p and miRNA-422a with osteoporosis in postmenopausal women.MethodsThis cross-sectional comparative study was performed on 126 randomly selected postmenopausal women aged 50-65, including 65 osteoporotic and 61 normal-bone mineral density (BMD) women. miRNA-21 and miRNA-422a were identified using qRT-PCR in these women. BMD was evaluated by the dual-energy X-ray absorptiometry method. A binary logistic regression model adjusted for confounders was used to evaluate the associations between plasma miRNAs' expression levels and osteoporosis. The Area Under Curve (AUC) was calculated to differentiate low BMD in the postmenopausal period using Receiver-Operator Characteristic (ROC) curves.ResultsmiRNA-21 and miRNA-422a were significantly up-regulated in osteoporotic compared to non-osteoporotic postmenopausal women. The expression levels of miRNA-21 and miRNA-422a indicated a significant reverse correlation with both lumbar spine and femoral neck density. After adjusting the confounders, the likelihood of osteoporosis in the postmenopausal women with under the median plasma levels of miRNA-21 (OR = 0.025; 95% CI: 0.003 to 0.198, p<0.001) and miRNA-422a (OR = 0.037; 95% CI: 0.007 to 0.211, p<0.001) was significantly less than the women with the levels above the median. There were significant inverse correlations between miRNA-21 (p<0.001, r = -0.511) and miRNA-422a (p<0.001, r = -0.682) with BMD-lumbar spine as well as an inverse correlation between miRNA-21(p<0.001, r = -0.374) and miRNA-422a (p<0.001, r = -0.602) with BMD-femoral neck. The AUC (95%CI) for miRNA-21 and miRNA-422a was 0.84 (0.77 to 0.91) and 0.98 (0.96 to 0.99), respectively. ROC analysis illustrated that sensitivity and specificity values were 83.1% and 74%, respectively, for miRNA-21 at the cut-off point of 3.38. Also, at the cut-off point of 2.86, a sensitivity of 94% as well as a specificity of 89% was determined for miRNA-422a.ConclusionsThis study indicated that the odds of osteoporosis in postmenopausal women increased with the higher expression of plasma miRNA-21 and miRNA-422a.

Project description:BackgroundAs one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis.MethodsExosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes.ResultsHsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1.ConclusionsExosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p.

Dataset Information

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

Background

Methodology/principal findings

Conclusions/significance

Publications

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

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