Serum microRNA signatures are indicative of skeletal fractures in post-menopausal women with and without type 2 diabetes and influence osteo-genic differentiation of mesenchymal stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70318 | GEO | 2016/12/31
SECONDARY ACCESSION(S): PRJNA288304
REPOSITORIES: GEO
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Project description:To explore the variation of serum microRNA expression during osteoporosis, we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs with the potential to diagnose osteoporosis from healthy and osteopenia individuals for clinical use. Whole blood from healthy, osteopenic and osteoporotic donors was collected, and the sera were separated. Twenty two microRNAs (miR-15a-5p, miR-29b-5p, miR-30c-2-3p, miR-145-5p, miR-199a-5p, miR-301a-3p, miR-424-5p, miR-497-5p, miR-526b-5p, miR-550a-5p, miR-575, miR-654-5p, miR-663a, miR-708-5p, miR-877-3p, miR-1246, miR-1260b, miR-1299, miR-1323, miR-4447, miR-4769-3p and miR-5685) were finally used for further detection of osteoporosis diagnosis.
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Project description:Breast Cancer is the cancer with most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients versus 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based upon the expression levels of 5 microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the over-expression and down-regulation of proteins differently expressed in the serum of breast cancer patients versus that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a-5p, mir-497-5p, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of mir-125b-5p, miR-29c-3p, mir-16-5p, miR-1260, and miR-451a was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of mir-16-5p with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and use of the predictor here described might be of potential importance for breast cancer prediction.
2020-09-18 | PXD020795 | Pride
Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients.
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Project description:Background: The identification of new high sensitivity and specificity markers for HCC are essential. We aimed to identify serum microRNAs for diagnosing hepatitis B virus (HBV) â??related HCC. Methods: Serum microRNA expression was investigated with four cohorts including 667 participants (261 HCC patients ,233 cirrhosi patients and 173 healthy controls), recruited between August 2010 and June 2013. First, An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls,respectively. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n=357) and then validated using a cohort(n=241). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: , We identified 8 miRNAs(hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p and hsa-miR-26a-5p.) formed a miRNA panel that provided a high diagnostic accuracy of HCC (AUC=0.887 and 0.879 for training and validation data set, respectively). The microRNA panel can also differentiate HCC from healthy (AUC =0.894) and cirrhosis (AUC = 0.892), respectively. Conclusions:We found a serum microRNAs panel that has considerable clinical value in diagnosing HCC. 9 serum samples pooled from 3 healthy control donors and 3 HCC patients, 3 cirrhosi patients treated at The First Affiliated Hospital of Soochow University were subjected to Illumina HiSeq 2000 deep sequencing to identify the miRNAs that were significantly differentially expressed.
2015-12-20 | E-GEOD-59418 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n=6) or osteoarthritis in the absence of osteoporosis (Control group, n=6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n=4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and non-osteoporotic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone.In conclusion, we identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy.
2015-12-21 | GSE74209 | GEO
Project description:This study aims to identify specific miRNAs profiles in osteoporotic patients with and without vertebral fractures. MiRNAs array analysis was performed on the plasma samples including a pool of 6 miRNA samples from osteoporotic patients with vertebral fractures, a pool of 6 miRNA samples from osteoporotic patients without fracture and another pool of 6 miRNA samples from nonosteoporotic patients to identify regulated miRNAs in the plasma.
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Project description:Background: The identification of new high sensitivity and specificity markers for HCC are essential. We aimed to identify serum microRNAs for diagnosing hepatitis B virus (HBV) –related HCC. Methods: Serum microRNA expression was investigated with four cohorts including 667 participants (261 HCC patients ,233 cirrhosi patients and 173 healthy controls), recruited between August 2010 and June 2013. First, An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls,respectively. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n=357) and then validated using a cohort(n=241). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: , We identified 8 miRNAs(hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p and hsa-miR-26a-5p.) formed a miRNA panel that provided a high diagnostic accuracy of HCC (AUC=0.887 and 0.879 for training and validation data set, respectively). The microRNA panel can also differentiate HCC from healthy (AUC =0.894) and cirrhosis (AUC = 0.892), respectively. Conclusions:We found a serum microRNAs panel that has considerable clinical value in diagnosing HCC.
2015-12-20 | GSE59418 | GEO
Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.
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Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (pancreatic cancer, hypopharyngeal squamous cell carcinoma and prostate cancer) were subjected to Agilent whole genome microarrays. Human cell lines (Panc-1, FaDu and PC3) were treated with miRNAs (miR99a-5p, miR-99a-3p, miR-100-3p, miR-150-5p and miR-150-3p), siRNAs (si-FOXQ1).
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