Showing papers by "Thomas D. Schmittgen published in 2007"
TL;DR: It is proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells, and the findings argue that ncRNAs and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.
736 citations
TL;DR: This study provides the first feasible biochemical mechanism by which the +1166 A/C polymorphism can lead to increased AT1R densities and possibly cardiovascular disease.
253 citations
TL;DR: The identification of signatures associated with diagnosis, prognosis and response to treatment of human tumors and miRNAs fingerprinting represents a new addition to the tools to be used by medical oncologists.
Abstract: MicroRNAs (miRNAs) represent a new class of small noncoding RNAs (ncRNAs, RNAs that do not codify for proteins) that can regulate gene expression by targeting messenger RNAs of protein coding genes and other ncRNA transcripts. miRNAs were recently found to be involved in the pathophysiology of all types of analyzed human cancers mainly by aberrant gene expression. This is characterized by abnormal levels of expression for mature and/or precursor miRNA transcripts in comparison to the corresponding normal tissues. miRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumors. Therefore, miRNAs fingerprinting represents a new addition to the tools to be used by medical oncologists.
215 citations
TL;DR: The authors' global analysis of predicted miRNA targets suggests that co-expressed miRNAs collectively provide systemic compensatory response to the abnormal phenotypic changes in cancer cells by targeting a broad range of functional categories and signaling pathways known to be affected in a particular cancer.
Abstract: Multiple recent studies have found aberrant expression profiles of microRNAome in human cancers. While several target genes have been experimentally identified for some microRNAs in various tumors, the global pattern of cellular functions and pathways affected by co-expressed microRNAs in cancer remains elusive. The goal of this study was to develop a computational approach to global analysis of the major biological processes and signaling pathways that are most likely to be affected collectively by co-expressed microRNAs in cancer cells. We report results of computational analysis of five datasets of aberrantly expressed microRNAs in five human cancers published by the authors (pancreatic cancer) and others (breast cancer, colon cancer, lung cancer and lymphoma). Using the combinatorial target prediction algorithm miRgate and a two-step data reduction procedure we have determined Gene Ontology categories as well as biological functions, disease categories, toxicological categories and signaling pathways that are: targeted by multiple microRNAs; statistically significantly enriched with target genes; and known to be affected in specific cancers. Our global analysis of predicted miRNA targets suggests that co-expressed miRNAs collectively provide systemic compensatory response to the abnormal phenotypic changes in cancer cells by targeting a broad range of functional categories and signaling pathways known to be affected in a particular cancer. Such systems biology based approach provides new avenues for biological interpretation of miRNA profiling data and generation of experimentally testable hypotheses regarding collective regulatory functions of miRNA in cancer.
74 citations
Patent•
02 Mar 2007TL;DR: In this article, the level of at least one miR gene product in a biological sample derived from the subject's pancreas was determined to be indicative of the subject either having, or being at risk for developing, pancreatic cancer.
Abstract: Methods are provided for diagnosing whether a subject has, or is at risk of developing, pancreatic cancer. The methods include measuring the level of at least one miR gene product in a biological sample derived from the subject's pancreas. An alteration in the level of the miR gene product in the biological sample as compared to the level of a corresponding miR gene product in a control sample, is indicative of the subject either having, or being at risk for developing, pancreatic cancer.
63 citations
TL;DR: Fluorescent ligand endocytosis assays showing colocalization between rhodamine-riboflavin and the immunostained caveolar coat protein, caveolin 1, suggest that the active absorption of this important nutrient involves multiple and distinct endocyTosis pathways.
Abstract: Riboflavin is thoroughly established to be indispensable in a multitude of cellular oxidation-reduction reactions through its conversion to coenzyme forms flavin mononucleotide and flavin adenine dinucleotide. Despite its physiological importance, little is known about specific mechanisms or proteins involved in regulating its cellular entry in humans. Studies involving biochemical modulators and immunological inhibition assays have indirectly revealed that riboflavin internalization and trafficking occurs at least in part through a clathrin-dependent receptor-mediated endocytic process. Here, using a two-tiered strategy involving RNA interference and the overexpression of dominant-negative constructs, we directly show the involvement of this endocytic mechanism through the requirement of the pluripotent endocytic vesicle scission enzyme, dynamin 2 GTPase, in human placental trophoblasts. Similar to the endocytic control ligand, transferrin, riboflavin is shown to exhibit 50% dependence on the functional expression of dynamin 2 for its active cellular entry. Furthermore, this reduced vitamin uptake correlates with >2-fold higher riboflavin association at the cell surface. In addition, fluorescent ligand endocytosis assays showing colocalization between rhodamine-riboflavin and the immunostained caveolar coat protein, caveolin 1, suggest that the active absorption of this important nutrient involves multiple and distinct endocytosis pathways.
18 citations
TL;DR: It is demonstrated that microRNA-124a is frequently silenced by epigenetic mechanisms in AML, becomes upregulated following epigenetic treatment and targets the C/EBPα 3′-untranslated region (3′UTR) in a posttranscriptional manner.
1 citations
Patent•
02 Mar 2007
TL;DR: The authors concerne des procedes for diagnostiquing the presence ou le risque du cancer de pancreas chez un sujet, by modifying the taux de produit genique miR dans l'echantillon biologique.
Abstract: L'invention concerne des procedes pour diagnostiquer la presence ou le risque du cancer de pancreas chez un sujet. Les procedes comprennent la mesure des taux d'au moins un produit genique miR dans un echantillon biologique derive du pancreas d'un sujet. Une alteration du taux de produit genique miR dans l'echantillon biologique en comparaison au taux de produit genique miR dans un echantillon de reference indique la presence ou le risque du cancer de pancreas chez le sujet.