1,721,012 research outputs found
Role and regulation of miR-483 in cancer
No full textThe hsa-mir-483 locus is located at chromosome 11p15.5 within intron 2 of the IGF2 locus. Because of its location, de-regulated in Wilms’ tumor and other neoplasia, I hypothesized that this microRNA had a potential role in tumors. By analyzing 19 Wilms’ tumors, I proved that miR-483-3p is indeed over-expressed in 100% of the cases and a co-regulation with the over-expression of IGF2 was found.
However, several other types of common adult cancers exhibit high or even extremely high levels of miR-483-3p expression without IGF2 over-expression. Indeed, independently from IGF2, the expression of the miR-483-3p could also be induced by the oncoprotein β-catenin through a novel interaction with the basic Helix-Loop-Helix protein upstream stimulatory transcription factor 1 (USF1).
I also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulative loop that becomes ineffective in cells harbouring activating mutations of β-catenin pathway.
The potential oncogenic role of miR-483-3p was supported by the findings that its ectopic expression protects cells from apoptosis and, conversely, its inhibition increase the level of apoptosis. To understand the mechanisms of its action, I investigated potential gene targets. Among these, an important pro-apoptotic protein, Puma, were inhibited by miR-483-3p. My results indicate that miR-483-3p functions as an anti-apoptotic oncogene, coordinately over-expressed with IGF2 in Wilms’ tumors or induced by β-catenin activation in other tumor types
Micro-markers: microRNAs in cancer diagnosis and prognosis
No full textMolecular diagnostics in cancer should provide the highest specificity and sensitivity in classification, prognostic stratification and early detection. MicroRNAs could contribute to hit the mark, or at least to come nearer, in virtue of their cancer-specific expression and stability. Indeed, differently from other RNA classes, microRNAs can be detected and quantified not only in frozen tissues, but also in formalin fixed paraffin-embedded tissues as well as serum/plasma samples. Thus, microRNA studies have quickly moved from research on the molecular basis of cancer to areas of clinical application. This review summarizes the potential role of microRNAs as molecular markers for cancer classification, prognostic stratification and drug-response prediction. It also summarizes their potential as circulating markers and cancer-predisposing genes. If we consider that studies on microRNAs in cancer therapy have already given important contributions, microRNAs already had an impact in all cancer areas. Whether this will translate into clinical applications is still too early to say. However, in the diagnostic field, microRNAs may already represent an improvement over presently available approaches: for example, their expression profile is effective in the identification of metastasis tissue of origin. In addition, circulating microRNAs are expected to provide improved specificity and/or sensitivity over presently available markers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Non-coding RNAs in the reprogramming of glucose metabolism in cancer
No full textProliferating cancer cells reprogram their metabolic circuitry to thrive in an environment deficient in nutrients and oxygen. Cancer cells exhibit a higher rate of glucose metabolism than normal somatic cells, which is achieved by switching from oxidative phosphorylation to aerobic glycolysis to meet the energy and metabolites demands of tumour progression. This phenomenon, which is known as the Warburg effect, has generated renewed interest in the process of glucose metabolism reprogramming in cancer cells. Several regulatory pathways along with glycolytic enzymes are responsible for the emergence of glycolytic dependence. Non-coding (nc)RNAs are a class of functional RNA molecules that are not translated into proteins but regulate target gene expression. NcRNAs have been shown to be involved in various biological processes, including glucose metabolism. In this review, we describe the regulatory role of ncRNAs–specifically, microRNAs and long ncRNAs–in the glycolytic switch and propose that ncRNA-based therapeutics can be used to inhibit the process of glucose metabolism reprogramming in cancer cells
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
KVDMR1, A LOCUS FREQUENTLY HYPOMETHYLATED IN HUMAN CANCER, IS A STRONG ENHANCER-PROMOTER ELEMENT FOR THE EXPRESSION OF LIT1, AN UNTRANSLATED IMPRINTOR GENE AT CHROMOSOME 11p15.5.
No full textAnticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag
No full textThe human polyomavirus BK (BKV) is oncogenic in rodents and induces malignant transformation of rodent cells in vitro. Although its role in human tumorigenesis is still debated, BKV represents an excellent model to evaluate molecularly targeted antineoplastic approaches. Here, we have tested whether stable suppression of the T antigen (T-ag) oncogene expression could inhibit the in vitro and in vivo malignant phenotype of BKV-transformed mouse cells. An adenovirus vector system that expresses small hairpin RNAs (shRNAs), which are converted into active small interfering RNAs (siRNA) molecules against the BKV T-ag, was developed. This vector was able to inhibit the expression of BKV T-ag through a highly efficient in vitro and in vivo delivery of the siRNA molecule. In addition, it allowed a stable expression of siRNA for a period of time sufficient to elicit a biological effect. Inhibition of T-ag expression results in reduction of the in vitro growth rate of BKV-transformed cells, which is, at least in part, caused by restoration of p53 activity and induction of apoptosis. In vivo studies proved that adenovirus vectors expressing anti-T-ag siRNA were able to suppress tumorigenicity of BKV-transformed cells. Moreover, adenovirus vector direct treatment of growing tumors resulted in a significant reduction of tumor growth. This study indicates that siRNAs delivery via a viral vector have a potential usefulness as in vivo anticancer tool against viral and cellular oncogenes
Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD
No full textThe stromal interaction molecular 1 gene (STIM1) encodes a type I trans-membrane protein of unknown function, which induces growth arrest and degeneration of the human tumor cell lines G401 and RD but not HBL100 and CaLu-6, suggesting a role in the pathogenesis of rhabdomyosarcomas and rhabdoid tumors. Here, we describe the STIM1 genomic organization including the identification of the promoter region. The gene consists of 12 exons that span a region larger than 250 kb between the genes RRM1 and NUP98. Nucleotide sequences of all exon-intron boundaries were determined and oligonucleotide primers for the amplification of individual exons were designed. The promoter region was identified within a 1.8-kb SacI fragment at the 5' end of the gene. In vitro CpG methylation of the promoter region indicated that transcription can be downregulated by this mechanism. The genetic tools developed in the present work will help to determine whether pathogenetic mechanisms that associate STIM1 with tumorigenesis involve mutations in coding sequences and/or promoter, and whether methylation could determine STIM1 transcriptional down-regulation in tumor samples
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