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Identification of aberrant miRNA expression in multiple myeloma

ABSTRACT: To identify aberrant miRNAs involved in the pathogenesis of multiple myeloma, we performed miRNA expression profiling of a total of 27 samples consisting of 19 clinical specimens, 8 myeloma cell lines and 3 normal peripheral blood samples. The microarray data were analysed by GeneSpring Software v13.0. We had identified 1799 miRNAs, which were differentially expressed by >2.0 fold change at p<0.05. Out of 1799 miRNAs, 1791 and 8 of them were up-regulated and down-regulated, respectively in myeloma group compared to the normal control group. Expression of 2 miRNAs (miR-150-5p and miR-4430) were verified by real-time PCR using the same RNA samples (20-22 samples were used) using SYBR Green. The real-time PCR confirmed that the expression of the miRNAs were consistent with microarray data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73048 | GEO | 2017/06/05

SECONDARY ACCESSION(S): PRJNA296002

REPOSITORIES: GEO

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Project description:In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Dysregulation in expression of microRNAs (miRNAs) in various tissues has been linked to a wide spectrum of diseases, including Type 2 Diabetes mellitus (T2D). In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Using luciferase assay, we further demonstrated that miR-144 directly targets IRS1 and showed its effects on protein expression via immunocytochemistry. From this cross-sectional study in humans, we have identified signature miRNAs which could explain the pathogenesis of T2D. Whether miRNAs like miR-144 could be potential therapeutic targets for management of T2D will need to be explored by further mechanistic and functional studies.

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Identification of aberrant miRNA expression in multiple myeloma

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