Non-Coding RNA, Volume 1, Issue 1 (June 2015) – 7 articles , Pages 1-93

The number of papers dealing with new modus operandi or new biological functions of non-coding RNAs published in recent years has indeed exploded. A simple search for ‘non-coding RNA’ in Pubmed on 10 June 2015 yielded 128,649 articles, half of which were published in the last 10 years [1]. Every researcher in this field knows that he has something to learn and can discover new ideas, new concepts or new tools from studies made in models others than the ones used in its lab. The Scientific board of Non-Coding RNA publishes here its first Journal Club and highlights, in about hundred words, a selection of the most interesting papers published recently. We hope we will tease your curiosity and encourage you to read full papers outside of your research area that you may not have read otherwise. [...] Full article

Glioblastoma multiforme (GBM), the most common form of primary brain tumor, is highly resistant to current treatment paradigms and has a high rate of recurrence. Recent advances in the field of tumor-initiating cells suggest that glioblastoma stem cells (GSCs) may be responsible for GBM’s rapid progression, treatment resistance, tumor recurrence and ultimately poor clinical prognosis. Understanding the biologically significant pathways that mediate GSC-specific characteristics offers promises in the development of novel biomarkers and therapeutics. Long non-coding RNAs (lncRNAs) have been increasingly implicated in the regulation of cancer cell biological behavior through various mechanisms. Initial studies strongly suggested that lncRNA expressions are highly dysregulated in GSCs and may play important roles in determining malignant phenotypes in GBM. Here, we review available evidence on aberrantly expressed lncRNAs identified by high throughput microarray profiling studies in GSCs. We also explore the potential functional pathways by analyzing their interactive proteins and miRNAs, with a view to shed lights on how this novel class of molecular candidates may mediate GSC maintenance and differentiation. Full article

Non-coding RNAs, such as microRNAs and long non-coding RNAs, are important regulatory molecules which are corrupted in cancer, often in a tissue and stage specific manner. Accumulated data suggests that these promising biomarkers, may also form the basis of novel targeted therapeutic strategies. The role of exosomes in cancer development and metastasis pathways is also increasingly well described. These endosome derived extracellular vesicles which are trafficked horizontally between tumor cells, and vertically between tumor cells and the surrounding microenvironment, carry bioactive cargos, which can reprogram the phenotype of recipient cells with important oncogenic consequences. Exosomes are enriched with non-coding RNA content. Within exosomes, non-coding RNAs are secreted into the peripheral circulation and other bodily fluids where they are protected from enzymatic degradation by the surrounding phospholipid membrane. Exosomes are therefore a highly promising source of diagnostic and prognostic material in cancer. Furthermore, as exosomes are natural ncRNA carriers, they may be adapted for the purpose of drug delivery by the introduction of exogenous ncRNAs or by manipulating their endogenous ncRNA content. In the current review, we will explore these highly clinically relevant themes by examining the roles of exosomal ncRNAs in cancer diagnostics, prognostics and therapy. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the expression of target mRNAs. MicroRNA genes themselves are regulated through epigenetic mechanisms, such as histone modifications and/or DNA methylation of CpG islands. Aberrant CpG island methylation patterns are frequently associated with cancer and thus researching DNA methylation of miRNA genes is a topic of increased research interest. Large quantities of available data from various studies are fragmented and incomplete; therefore, integration was performed. Data from 150 articles revealed 180 miRNA genes shown to be regulated via DNA methylation in 36 cancer types. From the total of 2588 known mature miRNA 6.9% (180/2588) miRNAs have been shown to be epigenetically regulated by DNA methylation. 45.5% (82/180) of miRNA genes were shown to be methylated in at least two cancer types among them hsa-miR-34b, hsa-miR-34c and hsa-miR-34a were found to be silenced in 24, 21 and 17 cancer types, respectively. The other 54.4% (98/180) miRNA genes regulated by DNA methylation were found to be specific for a certain type of cancer and therefore represent specific biomarker potential. Because specific miRNAs have diagnostic, prognostic and therapeutic potential, the systematically review of the field offers an overview of the field and facilitates experiment planning, generation of more targeted hypotheses and more efficient biomarker and target development. Full article

The advent of the microRNAs in the early 1990s has proven to be a tremendously significant development within the purview of gene regulation. They participate in the regulation of a broad assembly of processes vital to proper cell function and the perturbation of these pathways following alteration of miRNA expression is strongly believed to contribute to the pathogenesis of cancer. This review provides a comprehensive overview of the miRNAs that have to date been well-characterized in the context of human breast neoplasia. Detailed discussion will center around their role in tumor initiation and progression, control of epithelial-mesenchymal transition (EMT), cancer stem cell formation, use as biomarkers in tissues and circulation, as well as their role in cancer treatment. In addition, attention will be given to topics which remain underexplored, such as miRNA control of cancer cell metabolism and the genomic/epigenetic origins underlying the preliminary disruption of miRNA expression in disease. This review will also address and attempt to resolve instances where discordant, inter-study findings have been reported (examples of which are replete in the literature) while also identifying bottlenecks hampering progress in miRNA research and other challenges that confront this fledgling but promising field of biomedical research. Full article

B2 RNA is a mouse non-coding RNA that binds directly to RNA polymerase II (Pol II) and represses transcription by disrupting critical interactions between the polymerase and promoter DNA. How the structural regions within B2 RNA work together to mediate transcriptional repression is not well understood. To address this question, we systematically deleted structural regions from B2 RNA and determined the effects on transcriptional repression using a highly purified Pol II in vitro transcription system. Deletions that compromised the ability of B2 RNA to function as a transcriptional repressor were also tested for their ability to bind directly to Pol II, which enabled us to distinguish regions uniquely important for repression from those important for binding. We found that transcriptional repression requires a pattern of RNA structural motifs consisting of an extended single-stranded region bordered by two stem‑loops. Hence, there is modularity in the function of the stem-loops in B2 RNA—when one stem‑loop is deleted, another can take its place to enable transcriptional repression. Full article

Dear colleagues and non-coding RNAs aficionados, you will probably ask 'why a new journal'?, these days when we are flooded not only by information of any type in any sector of our life, but also by so many new journals that come and disappear like comets in the summer sky! The answer is simple: because we believe that this field finally deserves to have a dedicated journal where its wide community will be able to communicate and exchange its latest findings in one centralized place. Moreover, with your outstanding contributions and by publishing papers that promulgate the 'thinking out of the box', we will be able to build a reputation for Non-Coding RNA to survive over the years to come. [...] Full article