MicroRNAs: new players in heart failure

MicroRNAs (miRNAs) are a class of non-coding small RNAs representing one of the most exciting areas of modern medical science. miRNAs modulate a large and complex regulatory network of gene expression of the majority of the protein-coding genes. Currently, evidences suggest that miRNAs play a crucial role in the pathogenesis of heart failure. Some miRNAs as miR-1, miR-133 and miR-208a are highly expressed in the heart and strongly associated with the development of cardiac hypertrophy. Recent data indicate that these miRNAs as well as miR-206 change their expression quickly in response to physical activity. The differential regulation of miRNAs in response to exercise suggests a potential value of circulating miRNAs (c-miRNAs) as biomarkers of physiological mediators of the cardiovascular adaptation induced by exercise. Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of miRNAs levels using techniques such as ‘miR mimics’ and ‘antagomiRs’ is becoming evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.     

Estrogen receptors: new players in diabetes mellitus

Diabetes mellitus type 2 is a systemic disease characterized by imbalance of energy metabolism, which is mainly caused by inadequate insulin action. Recent data have revealed a surprising role for estradiol in regulating energy metabolism and opened new insights into the role of the two estrogen receptors, ERalpha and ERbeta, in this context. New findings on gene modulation by ERalpha and ERbeta of insulin-sensitive tissues indicate that estradiol participates in glucose homeostasis by modulating the expression of genes that are involved in insulin sensitivity and glucose uptake. Drugs that can selectively modulate the activity of either ERalpha or ERbeta in their interactions with target genes represent a promising frontier in diabetes mellitus coadjuvant therapy.     

Centromere regulation: new players, new rules, new questions

Centromeres support the assembly of the kinetochore on every chromosome and are therefore essential for the proper segregation of sister chromatids during cell division. Centromere identity is regulated epigenetically through the presence of the histone H3 variant CENP-A. CENP-A regulation and incorporation specifically into centromeric nucleosomes are the matter of intensive studies in many different model organisms. Here we briefly review the current knowledge in centromere biology with a focus on Drosophila melanogaster and how these insights lead to new rules and challenges.     

Long non-coding RNAs: new players in ocular neovascularization

Pathological neovascularization are the most prevalent causes of moderate or severe vision loss. Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in numerous biological processes and complicated diseases. However, the role of lncRNAs in ocular neovascularization is still unclear. Here, we constructed a murine model of ocular neovascularization, and determined lncRNA expression profiles using microarray analysis. We identified 326 or 51 lncRNAs that were significantly either up-regulated or down-regulated in the vaso-obliteration or neovascularization phase, respectively. Based on Pearson correlation analysis, lncRNAs/mRNAs co-expression networks were constructed. GO enrichment analysis of lncRNAs-co-expressed mRNAs indicated that the biological modules were correlated with chromosome organization, extracellular region and guanylate cyclase activator activity in the vaso-obliteration phase, and correlated with cell proliferation, extracellular region and guanylate cyclase regulator activity in the neovascularization phase. KEGG pathway analysis indicated that MAPK signaling was the most significantly enriched pathway in both phases. Importantly, Vax2os1 and Vax2os2 were not only dynamically expressed in the vaso-obliteration and neovascularization phases, but also significantly altered in the aqueous humor of patients with neovascular age-related macular degeneration (AMD), suggesting a potential role of lncRNAs in the regulation of ocular neovascularization. Taken together, this study provided novel insights into the molecular pathogenesis of ocular neovascularization. The intervention of dysregulated lncRNA could become a potential target for the prevention and treatment of ocular vascular diseases.     

Genetics of male infertility: the new players

Approximately 10-15% of couples experience infertility and male factors contribute to half of these cases. It was usually thought that infertility cannot be transmitted, but accumulating evidence indicates that many cases are indeed caused by genetic defects, some inherited. The use of single nucleotide polymorphisms (SNP) arrays allowing to genotype the totality of the genome recently led to identify several genes which, when mutated, generate specific infertility phenotypes. With the tremendous progresses in high throughput sequencing techniques, we can expect many more new genes involved in fertility to be identified in the next years. For the patients concerned, these findings mean the possibility of an accurate diagnosis and improved prognosis. Furthermore, these data will lead to a better understanding of the molecular mechanisms underlying spermatogenesis and thus should contribute to identify and offer new therapeutic strategies for the treatment of infertility.     

Beyond HPV: Oncomirs as new players in cervical cancer

MicroRNAs (miRNAs) are a recently discovered family of 18-24 nucleotide non-coding RNAs that can negatively regulate target mRNAs. All studied multicellular eukaryotes utilize miRNAs to regulate basic cellular functions including proliferation, differentiation, and death. It is now apparent that abnormal miRNA expression is a common feature of human malignancies. This review discusses the various cancer-relevant miRNAs (oncomirs) especially in cervical tumorigenesis and the potential role of oncomirs as therapeutic agents and targets for the treatment of cervical cancer.     

NADPH oxidases: new players in TNF-induced necrotic cell death

Necrosis is a caspase-independent cell death process involving the generation of reactive oxygen species (ROS). In a recent issue of Molecular Cell, Kim et al. (2007) reported on a novel TNF receptor 1 necrotic signaling complex inducing TRADD- and RIP1-dependent recruitment and activation of the ROS-generating Nox1 NADPH oxidase complex.     

MiRNAs as new master players

Despite the quite recent discovery of microRNAs (miRNAs), its impact on biology is enormous. In fact miRNAs have been shown to act on almost every biological pathway, where they can modulate the expression of critical molecules and thus control the whole biological process. But how much do they impact cell behavior? Are they key players or just an additional way to control gene expression at the last step before protein synthesis?     

Important new players in secondary wall synthesis

Secondary walls in wood are the most abundant biomass produced by plants. Understanding how plants make wood is not only of interest in basic plant biology but also has important implications for tree biotechnology. Three recent papers report exciting findings regarding a group of novel glycosyltransferases (GTs) involved in secondary wall synthesis. Because little is known about genes involved in the synthesis of wood polysaccharides other than cellulose, the identification of these GTs is a breakthrough in the molecular dissection of wood formation.     

Sphingolipids,new players in plant signaling

Sphingolipids are a diverse group of compounds, some of which play important signaling roles in animals and yeast. Results from recent research suggest that not only do plants contain components present in animal sphingolipid signaling pathways but that they might also possess novel plant-specific sphingolipid signaling systems. We suggest that the time is ripe for an in depth investigation of the role of this enigmatic group of compounds in plants.     

Deoxyribozymes: new players in the ancient game of biocatalysis.

The repetitive and extraordinarily stable polynucleotide chains of DNA serve as an ideal storage system for genetic information. Although it is best known for its helical structure and relatively inert character, in vitro selection can be used to compel DNA to perform a surprising variety of chemical reactions. These artificial DNA enzymes or 'deoxyribozymes' generate large chemical rate enhancements and demonstrate precise substrate recognition, much like their protein and RNA counterparts. Recent studies with these prototypic deoxyribozymes indicate that DNA has a substantial untapped potential for intricate structure formation that could be exploited in novel chemical and biological catalysis.