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Recent evidences indicate that epigenetic changes play an important role in the transcriptional reprogramming of gene expression that characterizes cardiac hypertrophy and failure and may dictate response to therapy. Several data demonstrate that microRNAs (miRNAs) play critical roles both in normal cardiac function and under pathological conditions. Here we assessed, in in vivo rat models of myocardial infarction (MI) and ischemia-reperfusion (IR), the relationship between two miRNAs (miR-29a and miR-30c) and de novo methyltransferase (DNMT3a) which, altering the chromatin accessibility for transcription factors, deeply impacts gene expression. We showed that the levels of members of miR-29 and miR- 30 families were down regulated in ischemic tissues whilst the protein levels of DNMT3a were increased, such a relation was not present in healthy tissues. Furthermore, by an in vitro assay, we demonstrated that both miRNAs are able to down regulate DNMT3a by directly interacting with DNMT3a 3’UTR and that miR-29a or miR-30c overexpression in the cardiac HL1 cell line causes decrease of DNMT3a enzyme both at the mRNA and protein levels. Our data, besides confirming the down regulation of the miR-29a and miR-30c in infarcted tissues, envisage a cross-talk between microRNAs and chromatin modifying enzymes suggesting a new mechanism that might generate the alterations of DNA methylation often observed in myocardial pathophysiology.
Small nucleolar RNAs (snoRNAs) are molecules located in the cell nucleolus and in Cajal bodies. Many scientific reports show that snoRNAs are not only responsible for modifications of other RNAs but also fulfill multiple other functions such as metabolic stress regulation or modulation of alternative splicing. Full-length snoRNAs as well as small RNAs derived from snoRNAs have been implied in human diseases such as cancer or Prader-Willi Syndrome. In this review we describe emerging, non-canonical roles of snoRNAs and their derivatives with the emphasis on their role in human diseases.
Content available remote miRNA function and modulation in stem cells and cancer stem cells
Stem cells belong to a unique class of cells that is collectively responsible for the development and subsequent maintenance of all tissues comprising multicellular organisms. These cells possess unique characteristics that allow them to remain in a pluripotent state, while also continuing to generate differentiated cells. microRNAs, a specialized class of non-coding RNAs, are integral components of the network of pathways that modulates this combination of abilities. This review highlights recent discoveries about the roles miRNAs play in governing stem cell phenotype, and discusses the potential therapeutic utility that miRNAs may have in the treatment of multiple diseases. Additionally, it addresses a novel mode of regulation of stem cell phenotype through lincRNA-mediated modulation of select miRNAs, and the role of secreted, stem cell-derived miRNAs in exerting a paracrine influence on surrounding non-stem cells.
The molecular basis for the formation and growth of vestibular schwannomas (VS) has been elucidated in the recent years. The main genetic and epigenetic aberrations, changes in gene expression and specific signaling pathways involved in pathogenesis of sporadic VS and neurofibromatosis type II (NF2) have been defined. These findings facilitated the search for prognostic markers in VS and potential targets for biological therapy. This publication summarizes the main directions of research in the field of molecular diagnostics and pharmacotherapy of VS based on biological agents.
Content available The process of microRNAs discovery
The widespread particularist account of the onset of molecular biology that identifies it with the discovery of the DNA structure in 1953 has been recently contested. The paper contributes to this debate by focusing on a more recent discovery of small noncoding RNAs (microRNAs). First, it outlines a particularist account of the microRNAs discovery and the origins of the particularist predilection of the modern scientometric studies of science dynamics. Next, it discusses its limitations and proposes an alternative, modified processualist account of the discovery. In the final part, the paper applies this approach to unravel network dynamics of the research on the first two microRNAs that were discovered, namely lin-4 and let-7.
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