5,003 research outputs found
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
MiR-27a/b inhibits aortic atherosclerosis.
No full textMale 8-week-old apoE KO mice (n = 10 mice per group) fed high fat diet were given a tail vein injection with miR-27a/b agomir negative control (AG-NC), miR-27a/b agomir (AGa/AGb), miR-27a/b antagomir negative control (AN-NC) and miR-27a/b antagomir (ANa/ANb). (A) MiR-27a/b alleviates atherosclerotic plaque development in apoE KO mice. Plaques (arrows) in aortic arches and thoracic aortas of representative apoE KO mice are shown. (B) Effects of miR-27a/b on atherosclerotic lesion areas in apoE KO mice. Representative images and the quantification of atherosclerotic lesion areas in the en face analysis of the whole aorta with Oil red O staining. (C) Effects of miR-27a/b on aortic atherosclerotic lesions in aortic root in apoE KO mice. Representative micrographs were obtained from hematoxylin-eosin staining of cross-sections of proximal aorta in apoE KO mice. (D) Effects of miR-27a/b on the aortic sinus lesion areas in apoE KO mice. Characterization of aortic sinus atherosclerotic lesion areas was performed by Oil red O staining. Total Oil red O staining positive area was determined using IMAGEPRO PLUS Software. Images of representative sections from each group are accompanied by summarized bar charts. Each data point represents an individual animal. The horizontal lines denote the mean of each group. All results are expressed as mean±S.D.*P<0.05 vs AG-NC. #P<0.01 vs AN-NC.</p
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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
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-190 enhances induction of Sima endogenous target genes.
No full textTranscript levels of two endogenous Sima target genes, fatiga B (fgaB) and heat shock factor (hsf), were analyzed by real time RT-PCR following overexpression of miR-190 or in miR-190KO embryos. Embryos were either kept in normoxia or exposed to mild hypoxia (8–11% O2) during 4 h. (A-B) miR-190 or miR-970 (negative control) were overexpressed ubiquitously using an act-Gal4 driver. (A) Both in normoxia and mild hypoxia, overexpression of miR-190 enhanced fgaB mRNA levels, as compared to control embryos bearing the act-Gal4 driver alone or overexpressing miR-970 as a negative control. (B) hsf transcript levels were increased in embryos overexpressing miR-190 in mild hypoxia. *ppost hoc test. Error bars represent SD; n ≥ 3 per group. (C-D) In mild hypoxia, expression of the Sima target genes (fgaB and hsf) was reduced in miR-190KO homozygous embryos, or in embryos heterozygous for miR-190KO and the rhea79a microdeletion. *ppost hoc test. Error bars represent SD; n ≥ 3 per group.</p
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
O papel de miR-21-3p e miR-146b-5p na patogênese do câncer papilar da tireoide
No full textO carcinoma papilífero de tireoide (CPT) é a neoplasia endócrina mais comum, responsável por 80-85% de todos os cânceres de tireoide e 1% de todas as neoplasias malignas humanas. Prever a evolução do CPT é um desafio atual para o manejo desse tipo de câncer. Embora o CPT geralmente tenha um bom prognóstico, uma fração dos pacientes apresentará comportamento agressivo com prognóstico ruim. Determinar o risco de um paciente desenvolver uma doença agressiva é útil para a adoção de estratégias de redução de risco de forma individualizada e personalizada. Recentemente, vários biomarcadores têm sido usados para determinar o risco de um indivíduo desenvolver câncer. MicroRNAs (miRNAs) podem regular muitas funções biológicas, como desenvolvimento celular, proliferação e transdução de sinais. Alterações na expressão de miRNAs são descritas em muitas doenças humanas, incluindo câncer. A expressão de miRNA é comumente desregulada no câncer e tornou-se um marco para o diagnóstico e prognóstico desta doença. No carcinoma de tireoide, estudos têm demonstrado que o perfil de expressão de miRNAs pode contribuir para predizer a evolução e o desfecho da doença. Neste estudo, realizamos algumas análises de bioinformática e ex vivo para explorar o papel de miR-21-3p e miR-146b-5p no contexto do CPT. Nossos dados apontam as vias associadas ao câncer MAPK, PI3K-AKT, Wnt, Notch, RAS e mTOR como alvos para miR- 21-3p e miR-146b-5p e observamos uma correlação positiva entre a expressão desses miRNA em amostras de CPT. Além disso, demonstramos expressão aumentada do miR-146b-5p em CPT e associação do miR-21-3p com características clínicas e oncológicas da doença. Esses fatos destacam a relevância de realizar uma análise prévia de possíveis interações por bioinformática, bem como investigar se os miRNAs podem impactar os desfechos clínicos de pacientes com CPT.Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, responsible for 80-85% of all thyroid cancer and 1% of all human malignancies. Predicting the evolution of PTC is a current challenge for cancer management. Although PTC generally has a good prognosis, a fraction of patients will exhibit aggressive behavior with a poor prognosis. Determining a patient's risk of developing an aggressive disease is useful for adopting risk reduction strategies in an individualized and personalized way. Recently, several biomarkers have been used to determine the risk of an individual developing cancer. MicroRNAs (miRNAs) can regulate many biological functions, such as cell development, proliferation, and signal transductions. Changes in miRNA expressions are described in many human diseases, including cancer. The miRNA expression is commonly deregulated in cancer and became hallmarks for the diagnosis and prognosis of this disease. In thyroid carcinoma, studies have demonstrated that the expression profile of miRNAs can contribute to predicting the disease evolution and outcome. In this study, we performed some bioinformatics and ex vivo analysis to explore the role of miR-21-3p and miR-146b-5p in the context of PTC. Our data point out the cancerassociated pathways MAPK, PI3K-Akt, Wnt, Notch, Ras, and mTOR as targets for miR-21- 3p and miR-146b-5p and we observed a positive correlation between these miRNA expressions in PTC samples. Additionally, we demonstrated upregulation of miR-146b-5p in PTC tumors and the association of the miR-21-3p with clinical and oncological features of the disease. These facts highlight the relevance of carrying out a prior analysis of possible interactions by bioinformatics, as well to investigate if these miRNAs could impact the clinical outcomes of PTC patients
miR-122 promotes virus-induced lung disease by targeting SOCS1
No full textVirus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations
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
Chili : Interview d’Ana L. Pinailillo, militante du MIR
No full textPinailillo Ana L., Briceno Louise. Chili : Interview d’Ana L. Pinailillo, militante du MIR. In: Cahiers du féminisme, n°22, 1983. Avortement : victoire partielle (décembre 1982 - janvier 1983) pp. 23-25
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