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Purpose: Craniopharyngiomas are benign tumors of the sellar or parasellar regions. They arise from the remnants of Rathke's pouch and are considered a "developmental disease." microRNAs are short non-coding RNAs that play a key regulatory role in the control of expression of entire gene networks. We performed an extensive analysis of miRNAs in craniopharyngiomas aiming to identify a miRNA expression signature that might aid in the prognosis of disease progression and outcome., Methods: Thirty-seven craniopharyngioma samples from twenty-three patients, ten age-matched controls from autopsy, and ten infant controls from the developing pituitary from autopsy were evaluated for the expression of 754 miRNAs using TaqMan® Low Density Arrays (TLDAs) v2.0 (Applied Biosystems, Foster City, CA)., Results: Among the most differentially expressed miRNAs, downregulation of miR-132 appears to be a marker of aggressiveness and also plays a role in epithelial-mesenchymal transition., Conclusions: This is the first time that an extensive study of miRNA expression has been performed in craniopharyngiomas. Further research needs to be performed to investigate the potential role of miR-132 in the development and progression of craniopharyngiomas, and its value as a prognostic marker of aggressiveness.

Objective: To identify differentially expressed microRNA (miRNA) in muscle biopsies (MBx) from 15 untreated children with juvenile dermatomyositis (JDM) compared with 5 controls., Methods: Following MBx miRNA profiling, differentially expressed miRNA and their protein targets were validated by quantitative real-time PCR (qRT-PCR) and immunological assay. The association of miRNA-10a and miRNA-10b with clinical data was evaluated, including Disease Activity Score (DAS), von Willebrand factor antigen (vWF:Ag), nailfold capillary end row loops, duration of untreated disease, and tumor necrosis factor (TNF)-α-308A allele., Results: In JDM, 16/362 miRNA were significantly differentially expressed [false discovery rate (FDR) < 0.05]. Among these, miRNA-10a was the most downregulated miRNA in both FDR and ranking of fold change: miRNA-10a = -2.27-fold, miRNA-10b = -1.80-fold. Decreased miRNA-10a and miRNA-10b expressions were confirmed using q, Rt-Pcr: -4.16 and -2.59 fold, respectively. The qRT-PCR documented that decreased miRNA-10a expression was related to increased vascular cell adhesion molecule 1 in 13 of these JDM cases (correlation -0.67, p = 0.012), unlike miRNA-10b data (not significant). Concurrent JDM plasma contained increased levels of interleukin (IL) 6 (p = 0.0363), IL-8 (p = 0.0005), TNF-α (p = 0.0011), and monocyte chemoattractant proteins 1 (p = 0.0139). Decreased miRNA-10a, but not miRNA-10b, was associated with the TNF-α-308A allele (p = 0.015). In the 15 JDM, a trend of association of miRNA-10a (but not miRNA-10b) with vWF:Ag and DAS was observed., Conclusion: MiRNA-10a downregulation is an important element in untreated JDM muscle pathophysiology. We speculate that muscle miRNA expression in adult dermatomyositis differs from muscle miRNA expression in untreated childhood JDM.

Purpose: Malignant rhabdoid tumors (MRT) can occur in a variety of anatomical sites. The most frequent locations are the brain, where they are named atypical teratoid/rhabdoid tumors (AT/RT), and the kidney, where they are named rhabdoid tumors of the kidney (RTK). MRTs at all sites are recognized as the same entity due to their similar morphology, aggressive behavior, and a common genetic abnormality, an inactivating mutation of the SMARCB1/INI-1/hSNF5/BAF47 gene. We aim to investigate potential molecular differences between AT/RT and RTK., Methods: We analyzed the microRNA (miRNA) and gene expression (GE) profiles of 10 RTK, 13 AT/RT, and 2 human MRT cell lines (G401-RTK and MON-AT/RT). Illumina V2 MicroRNA Chips (Illumina, Inc., CA, USA) were used for miRNA analysis, and Illumina HT-12 whole genome expression arrays were used for GE analysis., Results: The distribution of p values from GE showed a significant difference between RTK and AT/RT, with 20 % of the genes having p values ≤0.05 and the principal component analysis of the GE data showed separation between RTK and AT/RT. However, the miRNA expression failed to identify the different tumor groups. Among the 122 genes significantly differentially expressed between AT/RT and RTK, we found both genes related to brain development (i.e., FABP7, 22-fold increase in AT/RT) and genes related to kidney development (i.e., TCF21, sixfold increase in RTK)., Conclusion: Based on our results, we hypothesized that although MRT are indeed the same tumor, independent of the site of origin, the GE differences reflect the influence of microenvironment over tumor development.

Objective: To evaluate the effect of duration of untreated disease on vascular cell adhesion molecule 1 (VCAM-1) and microRNA (miRNA) expression in muscle biopsy samples from children with juvenile dermatomyositis (DM) as well as its effect on soluble VCAM-1 (sVCAM-1) and tumor necrosis factor α (TNFα) concentrations in sera from these children., Methods: We enrolled 28 untreated children with juvenile DM and 8 pediatric controls. Eleven children with juvenile DM had short duration of untreated disease (symptoms for ≤2 months before muscle biopsy), and 17 had long duration of untreated disease (symptoms for >2 months before muscle biopsy). Vascular structures, characterized by immunofluorescence using antibodies against von Willebrand factor, VCAM-1, and α-smooth muscle actin, were measured for total area and intensity. Circulating sVCAM-1 and TNFα levels were determined in patients with short duration of untreated disease, patients with long duration of untreated disease, and controls. Differential expression of microRNA-126 (miR-126) in muscle biopsy samples from the 2 patient groups and the control group was detected by miRNA expression profiling and confirmed by quantitative reverse transcription-polymerase chain reaction in muscle biopsy samples from the 3 groups., Results: Juvenile DM patients with short duration of untreated disease had significantly higher total positive area and intensity/high power field of VCAM-1 expression than did juvenile DM patients with long duration of untreated disease (P = 0.043 and P = 0.015, respectively) or controls (P = 0.004 and P = 0.001, respectively). Von Willebrand factor antigen-positive vasculature displayed greater VCAM-1 intensity in patients with short duration of untreated disease than in patients with long duration of untreated disease (P = 0.001). Circulating levels of sVCAM-1 and TNFα were significantly higher in patients with short duration of untreated disease than in controls (P = 0.013 and P = 0.048, respectively). The miRNA miR-126, a negative regulator of VCAM-1 expression, was significantly decreased (3.39-fold; P < 0.006) in patients with short duration of untreated disease compared to controls, while miR-126 expression in patients with long duration of untreated disease did not differ significantly compared to controls., Conclusion: In patients with short duration of untreated disease, miR-126 down-regulation is associated with increased VCAM-1 in both muscle and blood, suggesting that VCAM-1 plays a critical role early in juvenile DM disease pathophysiology, augmented by TNFα., (Copyright © 2012 by the American College of Rheumatology.)

Introduction: We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers., Materials and Methods: We have utilized TaqMan Low Density Arrays to evaluate the expression of 365 miRNAs in ependymomas and normal brain tissue. We first demonstrated the similarity of expression profiles of paired frozen tissue (FT) and paraffin-embedded specimens (FFPE). We compared the miRNA expression profiles of 34 FFPE ependymoma samples with 8 microdissected normal brain tissue specimens enriched for ependymal cells. miRNA expression profiles were then correlated with tumor location, histology and other clinicopathological features., Results: We have identified miRNAs that are over-expressed in ependymomas, such as miR-135a and miR-17-5p, and down-regulated, such as miR-383 and miR-485-5p. We have also uncovered associations between expression of specific miRNAs which portend a worse prognosis. For example, we have identified a cluster of miRNAs on human chromosome 14q32 that is associated with time to relapse. We also found that miR-203 is an independent marker for relapse compared to the parameters that are currently used. Additionally, we have identified three miRNAs (let-7d, miR-596 and miR-367) that strongly correlate to overall survival., Conclusion: We have identified miRNAs that are differentially expressed in ependymomas compared with normal ependymal tissue. We have also uncovered significant associations of miRNAs with clinical behavior. This is the first report of clinically relevant miRNAs in ependymomas.

Purpose: The aim of this study is to search for new therapeutic targets for atypical teratoid-rhabdoid tumors (ATRT)., Methods: To achieve this, we compared the expression of 365 microRNAs among ATRT, medulloblastomas, and normal brain., Results: MiR-221 and miR-222 were within the top differentially expressed microRNAs. The deregulated expression of miR221/222 was demonstrated to inhibit the expression of the tumor suppressor and inhibitor of cell cycle p27(Kip1). Here, we demonstrated the negative regulation of p27(Kip1) by miR-221/222 in ATRT using microarray, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry., Conclusion: As anti-miR therapy was recently proposed as an alternative treatment for cancer, these findings suggest that anti-miR-221/222 therapy might have therapeutic potential in ATRT.