2,730 research outputs found
MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells
No full textBackground: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods: Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results: Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC. Conclusions: These results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.Kayoko Matsushima... Gregory J Goodall... et al
Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway
No full textBackground: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. Methods: MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. Results: A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3’UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3’UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Conclusions: Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis
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Ali Husain Mir Interview
No full textAli Husain Mir is a Bollywood lyricist and script writer and a professor of Management at William Paterson University. Mir visited the Hindi Urdu Flagship at the University of Texas at Austin to speak to Flagship students about his career in Urdu literature and Bollywood production. For this interview, Mir sat down with HUF directors, Syed Akbar Hyder and Herman van Olphen, to discuss his background in Urdu and the state of the language in modern India. Mir is the author of Anthems of Resistance, the definitive book on the All India Progressive Writers’ Movement; he is also an acclaimed lyricist and script-writer for Hindi and Urdu films (Iqbal, Dor). Mir’s oeuvre engages issues of religious minorities and secularism in South Asia.Asian Studie
MiR-361-5p promotes proliferation and inhibits apoptosis of fibroblast-like synoviocytes <i>via</i> targeting ZBTB10 in rheumatoid arthritis
No full textThis study is aimed to explore the key role of miR-361-5p in fibroblast-like synovial (FLS) cells of rheumatoid arthritis (RA) and explore the underlying mechanism. First, we performed RT-qPCR to evaluate the expression of miR-361-5p in both synovial tissues of RA patients and cultured RA-FLS cells. Then CCK-8 assay, EdU staining, Western blot, flow cytometry, and ELISA were conducted to estimate the influence of inhibiting miR-361-5p on RA-FLS cells. Moreover, we used bioinformatics analysis to predict the potential targets of miR-361-5p and perform a dual luciferase report assay for verification. Finally, rescue experiments were performed to prove the role of miR-361-5p/Zinc Finger And BTB Domain Containing 10 (ZBTB10) in the proliferation, cell cycle, and apoptosis of RA-FLS. We find that the expression of miR-361-5p is increased in both RA tissues and cultured RA-FLS cells. The inhibition of miR-361-5p can not only inhibit proliferation, arrest the cell cycle in G1/G0 phase, and increase apoptosis, but also reduce the inflammatory factors secreted by RA-FLS cells. In addition, ZBTB10 is a direct target for miR-361-5p, over-expression of ZBTB10 reverses the effect of miR-361-5p in RA-FLS. MiR-361-5p promotes the progression of rheumatoid arthritis by targeting ZBTB10.Key pointsThe influences of miR-361-5p on RA-FLS cells. The influences of miR-361-5p on RA-FLS cells.</p
A rare SNP in pre-miR-34a is associated with increased levels of miR-34a in pancreatic beta cells
No full textChanges in the levels of specific microRNAs (miRNAs) can reduce glucose-stimulated insulin secretion and increase beta-cell apoptosis, two causes of islet dysfunction and progression to type 2 diabetes. Studies have shown that single nucleotide polymorphisms (SNPs) within miRNA genes can affect their expression. We sought to determine whether miRNAs, with a known role in beta-cell function, possess SNPs within the pre-miRNA structure which can affect their expression. Using published literature and dbSNP, we aimed to identify miRNAs with a role in beta-cell function that also possess SNPs within the region encoding its pre-miRNA. Following transfection of plasmids, encoding the pre-miRNA and each allele of the SNP, miRNA expression was measured. Two rare SNPs located within the pre-miRNA structure of two miRNA genes important to beta-cell function (miR-34a and miR-96) were identified. Transfection of INS-1 and MIN6 cells with plasmids encoding pre-miR-34a and the minor allele of rs72631823 resulted in significantly (p < 0.05) higher miR-34a expression, compared to cells transfected with plasmids encoding the corresponding major allele. Similarly, higher levels were also observed upon transfection of HeLa cells. Transfection of MIN6 cells with plasmids encoding pre-miR-96 and each allele of rs41274239 resulted in no significant differences in miR-96 expression. A rare SNP in pre-miR-34a is associated with increased levels of mature miR-34a. Given that small changes in miR-34a levels have been shown to cause increased levels of beta-cell apoptosis this finding may be of interest to studies looking at determining the effect of rare variants on type 2 diabetes susceptibility. © 2013 The Author(s)
miR-183 promotes radioresistance of lung adenocarcinoma H1299 cells via epithelial-mesenchymal transition
No full textLung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.</div
Maintaining Privacy During Psychosocial Research on the International Space Station
No full textConducting psychosocial research on the International Space Station (ISS) requires rigorous privacy precautions that exceed standard scientific human subject protocols. In our previous study involving crewmembers on Mir, and in our ongoing ISS work, special precautions were taken during each phase of the missions. Pre-flight, participants received detailed consent forms explaining that only group-level data would be presented, and they chose ID codes known only to them. In-flight, special procedures protected data during collection and transmission. Post-flight, our analytic strategy further masked participants’ identities, and participant representatives were invited to review manuscript drafts prior to publication. In this paper we describe lessons learned during our on-orbit studies and discuss their relation to maintaining privacy on studies of future long-duration space missions
MiR-124 overexpression time course analysis to identify predicted targets in total downregulated genes
No full text<p><b>Copyright information:</b></p><p>Taken from "Systematic identification of microRNA functions by combining target prediction and expression profiling"</p><p>Nucleic Acids Research 2006;34(5):1646-1652.</p><p>Published online 20 Mar 2006</p><p>PMCID:PMC1405822.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> () Counts of downregulated predicted targets at different time points after miR-124 transfections. () The percentages of predicted targets in total downregulated genes
MiR-28-3p regulates high glucose-induced endothelial dysfunction by targeting CXXC5
No full textIntroduction
Data from the CEO database show that microRNA (miR)-28-3p levels are elevated in diabetic patients. Nevertheless, the role of miR-28-3p in peripheral artery disease with diabetes has not been investigated.
Material and methods
The levels of miR-28-3p, CXXC5, CXXC-type zinc finger protein 5, and CXXC5’s downstream molecules as well as endothelial function were investigated. Dual luciferase analyses were used to confirm the binding site of miR-28-3p and CXXC5.
Results
Under high-glucose conditions, miR-28-3p expression is upregulated, whereas CXXC5 expression is downregulated. Overexpression of miR-28-3p increased cell apoptosis and inhibited cell proliferation, migration, and vessel formation, whilst inhibiting its expression had the opposite effect. The overexpression and inhibition of miR-28-3p could also influence both the mRNA and protein levels of CXXC5 and its known downstream molecules. Analysis of bioinformatics data revealed a potential binding site for miR-28-3p and CXXC5. Dual luciferase analyses demonstrated that miR-28-3p suppressed CXXC5 expression by targeting the 3-untranslated region (3-UTR) of CXXC5. Following that, we overexpressed both miR-28-3p and CXXC5. The level of CXXC5 and its known downstream signaling molecules decreased with miR-28-3p overexpression alone. As anticipated, co-overexpression of miR-28-3p and CXXC5 partially reversed the effect of miR-28-3p mimics.
Conclusions
These findings indicated that miR-28-3p regulated high glucose-induced endothelial dysfunction by targeting CXXC5
Regulating railways
No full textThis issue of Network Industries Quarterly will look at different issues of rail regulation with examples from in and outside the European Union. The rail sector in Europe like other network industries is in a process of organizational restructuring that is part of different forms of liberalisation as well as de- and re-regulation. In this process many approaches to railway regulation are reassessed. Achieving more, better and more cost efficient rail services for freight and passengers is a commonly shared goal, but there are different opinions on the right policies to achieve this goal. This issue of the Network Industries Quarterly will look at different aspects of rail regulation with examples from in and outside the European Union. On the example of the Swiss rail reform Desmaris looks at the relationship between competition and performance. Kuligowska describes the recent reforms that the Polish rail regulator had to undertake when dealing with open access provision. Laroche discusses the issue of congestion of railway lines and how saturation of rail infrastructure can be modelled. Thiebaud & Amaral look at how prices influence coordination in the rail sector. Peña-Alcaraz et al. present an alternative view on capacity pricing in open access rail systems on the case of Tanzania.-- The reform of passenger rail in Switzerland: more performance without competition?, Christian Desmaris - Institute of Political Studies, University of Lyon, France
-- Current regulatory challenges in access to the rail infrastructure in Poland, Izabela Kuligowska – Polish Office of Rail Transportation
-- Methods for saturation modelling of railway lines: the case of High-Speed Line Paris-Lyon, Florent Laroche - Institute of Political Studies, University of Lyon, France
-- Vertical Separation in Rail Transport: How Do Prices Influence Coordination?, Miguel Amaral, Jean-Christophe Thiebaud - French Railway Regulatory Body (ARAF) & EPPP Chair (Sorbonne Business School)
-- Capacity pricing schemes to implement open-access rail in Tanzania, Maite Peña-Alcaraz, Ignacio Perez-Arriaga, Joseph M. Sussman - Massachusetts Institute of Technology (MIT
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