miRNA Blog

OncomiRs: New miRNA & Cancer Focused Open Access Journal

Christoph — Fri, 18 May 2012 19:27:30 +0000

OncomiRs is a new open access journal from Emerging Science Journal program, launched recently by Versita.
The journal will publish original research articles and reviews covering all the basics aspects of the microRNAs implication in tumor formation and development as well as their role in the treatment sensitivity and resistance. The OncomiRs’ focus lies on the basic principles of microRNAs implication in the regulation of cellular processes like apoptosis, cell cycle control, metastatic dissemination, cellular senescence and immortalisation. A particular attention is given to microRNA-controlled regulation of cellular oncogenes and tumor suppressor genes.

The journal provides a unique opportunity for academics to highlight their research work in the single specialized microRNA and cancer research journal. Owing to Open Access model, manuscripts accepted for publication are immediately published on-line.

The implications of microRNAs in cancer biology is a topic that has emerged recently, but has already generated a considerable number of papers. The editors joined the efforts to position this journal as a natural publishing option for authors writing on oncomirs, and to establish it as a hub integrating the relevant research community. Key researchers have supported the journal as members of Editorial Advisory Board, among them: Prof.George Adrian Calin and Prof. Elsa Flores, both from University of Texas MD Anderson Cancer Center, USA; Prof. Clark Jeffries from University of North Carolina at Chapel Hill, USA or Prof. Adrian Harris from University of Oxford, United Kingdom.

Journal Editor – Prof. Benjamin Ory, from Nantes University School of Medicine is positive that the OncomiRs should become the central publication venue for scientists and clinicians active in the field of microRNAs biology and cancer research. He comments: ‘the journal will facilitate the sharing and dissemination of significant contributions and timely research in the emerging field of microRNAs in cancer. Publishing in open access will doubtlessly bring about increased readership and interest from scientists and scholars alike’.

http://www.versita.com/oncom/

International Workshop on Small RNA in Cancer Inflammation and Aging

Christoph — Thu, 10 May 2012 07:52:04 +0000

Dates: from 03 September 2012 12:00 to 04 September 2012 17:00
Timezone: Europe/Copenhagen
Location: Eigtveds Pakhus, Copenhagen, Denmark

Registration closes on August 24, 2012.
Abstract submissions are due by August 01, 2012

Confirmed speakers include: Aaron J. Schetter
Anders H. Lund
Carlo M. Croce
Curtis C. Harris
Hadi Valadi
Heiko Hermeking Henrik Ørum
Jan Gorodkin
Jørgen Kjems
Michael G. Katze
Zachary Pincus

Conference website:
http://indico.conferences.dtu.dk/conferenceDisplay.py?confId=114

More miRNA conferences

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MicroRNAs in Plants vs. Animals

Doug Dluzen — Thu, 10 May 2012 07:33:06 +0000

It is becoming increasingly clear that microRNA are important regulators of gene expression within the animal kingdom. However, microRNA are also found in plants, behaving more like small inhibiting RNA (siRNA) during target gene knockdown. A recent review published in Genome Biology aims to discuss the differences between animal and plant microRNA and highlights the important role of each within the two kingdoms. Axtell et al. serves to showcase the important similarities and differences between microRNA in separate kingdoms and uses the model plant organism Arabidopsis thaliana as an example of classic plant microRNA function. In plants, microRNA are transcribed by RNA polymerase II as in animals, but the entire process of microRNA biogenesis is undertaken within the plant nucleus. The mature microRNA are exported out of the nucleus by Hasty, an exportin 5-like protein found in plants. A major difference between plant and animal microRNA falls within target recognition. Axtell et al. reviews the target recognition process between plants and animals; notably the direct mRNA cleavage of a microRNA target in plants due to near-perfect base complementation between the microRNA and its target. This differs vastly in animals where protein repression is believed to occur by translation inhibition as well as mRNA degradation. Hybridization of microRNA to target in animals is less stringent near the 3’ end of the microRNA strand and relies on the canonical 7-8 nucleotide “seed sequence” to drive microRNA target recognition.

After highlighting the similarities and differences between plants and animals, the review dives into some evolutionally perspectives and driving factors of microRNA evolution in plants and animals. Interestingly, Axtell et al. discusses events that lead to the emergence of new microRNA genes in plants and animals. Briefly, it is more common in plants for microRNA genes to emergence via mechanisms of inverted duplication events, where as in animals it is more common for microRNA hairpins to evolve from mutational events in “unstructured” sequences of the genome. These evolutionary driving factors and mechanisms for newly acquired microRNA genes can perhaps help researchers identify novel microRNA targets within gene loci of interest. Even though most research in microRNA regulation of target genes is primarily focused on animal gene regulation, and specifically within human disease states, acknowledging the breadth and scope of microRNA regulation across kingdoms may provide useful insights into microRNA research.

Axtell, MJ., et al.
Vive la difference: biogenesis and evolution of microRNAs in plants and animals.
Genome Biology. 12(2011): p. 221-234.
http://genomebiology.com/2011/12/4/221

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sRNA Workbench Version 2.3.2 Released

Christoph — Thu, 12 Apr 2012 18:33:21 +0000

The sRNA Workbench is a Java based suite of tools for analyzing small RNA/miRNA data from Next Generation Sequencing devices. Latest version is 2.3.2 and was released yesterday.
The update covers several bug fixes and behavior modifications relating to all operating systems and several tools.

sRNA Workbench home page:
http://srna-workbench.cmp.uea.ac.uk/

Direct download link:
http://sourceforge.net/projects/srnaworkbench/

Changes and fixes in detail:

Adapter Removal

Adapter removal was inaccessible from the command line. This issue has now been resolved

miRCat:

miRCat was inaccessible from the command line. This issue has now been resolved
miRCat had an issue when creating large amounts of RNA annotation renders (when outputting to disk) potentially causing some entries in the legend to be missed. This has now been resolved
miRCat should now correctly output GFF records that can be read by any genome browser
When running miRCat from the command line, the mature miRNA sequences are now written to a file called miRNA.fa and stored in the output directory
When running miRCat from the command line a user no longer needs to have updated miRBase from the GUI first (however, if no miRBase files are detected then the tool will not be able to look for known miRNA sequences)

RNA annotation

RNA annotation was incorrectly colouring extra nt when the short sequences were overlapping the ends of the long sequences. This affected both the GUI and when activating the tool directly from miRCat, this should now work correctly
When rendering large amounts of hairpins to disk the hairpin tool would not show the hairpins (leaving them in the selected directory). This behaviour has been modified, the RNA annotation tool now has the ability to navigate directories of hairpin images including those generated by miRCat when rendering large amounts of results
Any RNA Annotation frames generated from miRCat when in file mode (i.e. when rendering large amounts of results) are locked to that specific directory and cannot have new hairpins added to them, however, new RNA annotation frames can be created in the usual way
A new window showing progress of RNA annotation renders from miRCat has been added
When rendering RNA plots directly from miRCat the colours of the highlighted regions (miRNA and miRNA*) should now match the highlighted text in the miRCat output table (blue for miRNA and red for miRNA*)
Rendering large amounts of hairpins has now been moved to a separate thread to prevent locking the main workbench thread
Hiding the sequence options in the tool will now also hide the colour palette
The labels in the colour chooser now change their colour to reflect the selected colour for the respective short sequence

General:

Changed logging level of certain messages from miRCat and RNA annotation to stop the printouts appearing in the console window when they are not needed
The menu system from the main window has been slightly overhauled to match the menu system on the website and in preparation for new tools coming soon

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miR-375 as Regulator of Key Immune Hormone IL-13 Identified

Christoph — Thu, 29 Mar 2012 06:06:41 +0000

CINCINNATI, March 28, 2012 /PRNewswire-USNewswire/ — Researchers have taken a critical step in understanding how allergic reactions occur after identifying a genetic signature for regulation of a key immune hormone, interleukin (IL-13).

Scientists from Cincinnati Children’s Hospital Medical Center say the finding opens the potential for new molecular targets to treat allergic disease. They report on March 28 in Mucosal Immunology that a particular microRNA, miR-375, is regulated by IL-13, and in turns regulates how IL-13 induces pro-allergic changes, particularly in epithelial cells in the lung and esophagus.

The data support a role for miR-375 in asthma and in eosinophilic esophagitis (EoE), a severe, often painful food allergy that renders children unable to eat a wide variety of foods. EoE can also cause weight loss, vomiting, heartburn and swallowing difficulties.

“The identification of a microRNA that regulates IL-13-induced changes and inflammatory pathways is a significant advancement for the understanding and future treatment of allergic disease,” says Marc E. Rothenberg, MD, senior investigator on the study and director of the Division of Allergy and Immunology and Center for Eosinophilic Disorders at Cincinnati Children’s. “MiR-375 is proof of principle that microRNAs are involved in fine-tuning IL-13-mediated responses, which opens up a set of new possibilities for novel therapeutic targets for treatment of allergic disease.”

IL-13 induces changes in epithelial gene and protein expression that are important in the onset of many allergic diseases, including EoE. Notably, expression of miR-375 was consistently downregulated after IL-13 stimulated human esophageal squamous and bronchial epithelial cells. Viral overexpression of miR-375 in epithelial cell cultures markedly modified the IL-13-associated immunoinflammatory pathways.

In the current study, investigators stimulated esophageal and bronchial human epithelial cells with IL-13 and analyzed for differential microRNA expression. Decreases in miR-375 were observed in the human cells and also in an IL-13 transgenic mouse model. The researchers subsequently assessed miR-375 in patients with EoE, a human allergic disease characterized by IL-13 overproduction, and in healthy individuals.

Interestingly, the researchers found that decreased expression of miR-375 correlates significantly with disease activity, the degree of allergic inflammation and that miR-375 expression normalizes with disease remission. While this suggests miR-375′s potential use as a disease activity biomarker for certain allergic diseases, changes in IL-13-mediated inflammatory pathways with viral overexpression of miR-375 in epithelial cell cultures also hint at its therapeutic potential.

Allergic diseases have been on the rise over the past 20 years, with approximately one of every 13 children having food allergies and over 2.5 million children suffering from allergic asthma. Only recently recognized as a distinct condition, the incidence of EoE has also been increasing. Rothenberg and his laboratory team pioneered research showing EoE’s reported incidence is estimated to be at least one in 1,000 people. Its hallmark is swelling and inflammation in the esophagus, accompanied by high levels of immune cells called eosinophils.

EoE can affect people of any age, but is more common among young men who have a history of other allergic diseases, such as asthma and eczema. EoE is often first discovered in children with feeding difficulties and failure to thrive, but it is often misunderstood and not well known, delaying proper diagnosis and treatment.

Funding support for the study came from the National Institutes of Health, the Campaign Urging Research for Eosinophilic Disease (CURED), the Food Allergy Initiative (FAI), and the Buckeye Foundation.

The Rothenberg Lab

http://www.cincinnatichildrens.org/research/divisions/a/allergy-immunology/labs/rothenberg/default/

SOURCE Cincinnati Children’s Hospital Medical Center

MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome
T X Lu, E-J Lim, T Wen, A J Plassard, S P Hogan, L J Martin, B J Aronow and M E Rothenberg
Mucosal Immunology advance online publication 28 March 2012; doi: 10.1038/mi.2012.16

http://www.nature.com/mi/journal/vaop/ncurrent/full/mi201216a.html

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Genetic Marker for Painful Food Allergy Points to Improved Diagnosis, Treatment

Christoph — Fri, 09 Mar 2012 19:54:33 +0000

CINCINNATI, March 9, 2012 /PRNewswire-USNewswire/ – Researchers have identified a genetic signature for a severe, often painful food allergy – eosinophilic esophagitis – that could lead to improved diagnosis and treatment for children unable to eat a wide variety of foods.

The scientists, from Cincinnati Children’s Hospital Medical Center, report in the Journal of Allergy and Clinical Immunology that they have pinpointed a dysregulated microRNA signature for eosinophilic esophagitis (EoE), a disease that also may cause weight loss, vomiting, heartburn and swallowing difficulties.

Interestingly, the dysregulated microRNA was reversible with steroid treatment, according to the study’s senior investigator, Marc E. Rothenberg, MD, PhD, director of Allergy and Immunology and the Center for Eosinophilic Disorders at Cincinnati Children’s. MicroRNAs are short segments of RNA that can regulate whether genetic messengers (mRNAs) are degraded or translated into protein.

“The identification of biomarkers specific to EoE is a significant advancement for both the diagnosis and treatment of the disease,” explains Rothenberg. “The microRNA signature provides an opportunity for more precise analysis of esophageal biopsies.”

Rothenberg said children with EoE now undergo anesthesia and invasive endoscopy to diagnose and monitor the allergy. The ability to determine the presence and status of EoE with a noninvasive method, such as blood test that measures microRNAs, would have a positive impact on individuals and families.

In the current study, investigators analyzed esophageal microRNA expression of patients with active EoE, steroid-induced EoE remission, patients with chronic (non-eosinophilic) esophagitis and of healthy individuals. Additionally, they assessed plasma microRNA expression of patients with active EoE, remission of EoE remission and of healthy individuals.

The researchers found that EoE was associated with 32 differentially regulated microRNAs and distinguishable from the non-eosinophilic forms of esophagitis (such as reflux disease). Esophageal eosinophil levels correlated significantly with expression of the most increased microRNAs, miR-21 and miR-223, and most decreased, miR-375. MiR-223 was also one of the most increased microRNAs in the plasma, along with miR-146a and miR-146b.

Notably, the expression of microRNAs dysregulated in patients with active EoE was normalized in patients with EoE who responded to steroid treatment. This suggests a significantly specific microRNA signature for disease activity points to its promise for use as a biomarker for EoE.

Only recently recognized as a distinct condition, the incidence of EoE has been increasing over the past 20 years, as have other allergies. Rothenberg and his laboratory team pioneered research showing EoE’s reported incidence is estimated to be at least one in 1,000 people. Its hallmark is swelling and inflammation in the esophagus, accompanied by high levels of immune cells called eosinophils.

Several organizations provided funding support for the study, which was released online March 3. These include the National Institutes of Health, the Campaign Urging Research for Eosinophilic Disease (CURED), the Food Allergy Initiative (FAI), and the Buckeye Foundation.

About Cincinnati Children’s

Cincinnati Children’s Hospital Medical Center is one of eight children’s hospitals named to the Honor Roll in U.S. News and World Report’s 2010-11 Best Children’s Hospitals. It is ranked #1 for digestive disorders and highly ranked for its expertise in pulmonology, cancer, neonatology, heart and heart surgery, neurology and neurosurgery, diabetes and endocrinology, orthopedics, kidney disorders and urology. Cincinnati Children’s is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for quality and transformation work by Leapfrog, The Joint Commission, the Institute for Healthcare Improvement, the federal Agency for Healthcare Research and Quality, and by hospitals and health organizations it works with globally. Additional information can be found at www.cincinnatichildrens.org.

The Rothenberg Lab
https://www.facebook.com/RothenbergEosinophilicLab

The Cincinnati Center for Eosinophilic Disorders
https://www.facebook.com/CCEDeos

Cincinnati Children’s Hospital Medical Center
https://www.facebook.com/cincinnatichildrensfans

SOURCE Cincinnati Children’s Hospital Medical Center

CONTACT: Jim Feuer, +1-513-636-4656

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers
Thomas X. Lu, Joseph D. Sherrill, Ting Wen, Andrew J. Plassard, John A. Besse, Juan Pablo Abonia, James P. Franciosi, Philip E. Putnam, Michael Eby, Lisa J. Martin, Bruce J. Aronow, Marc E. Rothenberg
The Journal of allergy and clinical immunology 5 March 2012 (Article in Press DOI: 10.1016/j.jaci.2012.01.060)

http://www.jacionline.org/article/S0091-6749%2812%2900188-1/abstract

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Expression of mRNA and miRNA in Different Neuronal Cell Types

Doug Dluzen — Thu, 08 Mar 2012 13:23:04 +0000

Recent research published in Gene investigates the relationship between mRNA and miRNA expression levels in different neuronal cell types and neuroblastoma. Using microarray analysis coupled with EGAN (Exploratory Gene Association Networks) software, Liu et al. studied the mRNA-miRNA expression relationships between three neuronal cell types: mature neurons and neural progenitor cells (derived from rat brain tissue) and neuroblastoma cells. The authors concluded that there are expression signatures of mRNA and miRNA transcripts characteristic of each of the different cell types. Most of the over-expressed mRNA transcripts found in mature neurons had low levels of expression in neuroblastoma cells and moderate expression in progenitor cells. The authors found this pattern to be true for transcripts over-expressed in neuroblastoma cells as compared to mature neurons, and that the pathways represented by the over-expressed transcripts in neuroblastoma were related to pathways specific to cancer. The results indicated that a portion of over-expressed mRNA transcripts in mature neuronal cells (or neuroblastoma cells) also had under-expressed miRNA species (within the same cell type) that are predicted to target the over-expressed mRNAs. Validation studies of specific mRNA-miRNA interactions were not reported in this article. The authors conclude their discussion by commenting on the possibility of mRNA-miRNA regulatory network signatures as a tool to identify novel tumor suppressor candidates.

These findings contribute to the growing list of evidence supporting the role of miRNA in cancer regulation as well as in normal tissue development. Liu et al. highlight the proposed interaction between tumor-associated factor Runx1 and miR-370. The expression of Runx1 and miR-370 is inversely proportional in neuroblastoma cells (high Runx1, low miR-370) and mature neurons (low Runx1, high miR-370) with moderate expression of both in neuroprogenitor cells. Their analysis did not confirm the direct regulation of Runx1 mRNA by miR-370, but the network analysis provided in this study may be able to lay the groundwork to isolate important miRNA candidates which are deregulated in neuronal cancers. Liu et al. shine some light onto the potential of studying miRNA regulation in normal tissue development as a mechanism of learning about normal, functioning pathways which become aberrantly regulated in cancer initiation and progression. Considering the relatedness of normal tissue development and cancer signaling, identifying novel miRNA networks in these two pathways (particularly normal tissue development) can contribute to our further understanding of cancer mechanisms.

Liu, Da-Zhi., et al.
Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells.
Gene. 495(2012): p. 120-127.
http://www.sciencedirect.com/science/article/pii/S0378111911008250

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Java based sRNA workbench for analysing small RNA data from Next Generation Sequencing devices

Christoph — Thu, 08 Mar 2012 08:25:21 +0000

The UEA sRNA workbench was developed by the Moulton group at the University of East Anglia and is a new simple to use, downloadable, Java based sRNA software package. It is based on algorithms developed for the 2008 released original UEA sRNA Toolkit. The software will perform a complete analysis of single or multiple-sample sRNA datasets from both plants and animals to identify interesting landmarks (such as detection of novel miRNA sequences) in genetic data. The latest Version 2.3.1 (Released: March 9^th 2012) includes now the PAREsnip tool which allows to find targets of small RNAs using the degradome. For more see the PAREsnip page.

Currently, the downloadable version of the UEA sRNA workbench contains a subset of the web-based sRNA toolkit functionality. The later is still available for animal as well as plant and both version can be accessed from the main UEA sRNA toolkit site.

The UEA sRNA workbench is available for download at: srna-workbench.cmp.uea.ac.uk

citation for the original version:
S. Moxon, F. Schwach, D. MacLean, T. Dalmay, D. J Studholme, and V. Moulton
A toolkit for analysing large-scale plant small RNA datasets.
Bioinformatics 2008

http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btn428

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Microcosmos of Cancer: A Mini Review

Doug Dluzen — Tue, 21 Feb 2012 17:01:54 +0000

In this week’s issue of Nature , two researchers at the Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center have published a review discussing the diverse contribution microRNA networks exhibit in cancer biology. Lujambio et. al. discuss both the oncogenic and tumor-suppressor roles microRNA have been attributed in the initiation and progression of multiple cancers. Discussion also focuses on microRNA as a driving/initiation factor in tumor biology and provides a thorough review of the dynamic between several microRNA genes and the TP53 tumor suppressor. The mouse model system is highlighted as a very useful tool validating and investigating the in vivo role specific microRNA contribute to tumor development and risk. The review concludes with a discussion concerning the potential roles of RNAi technology and its use as a therapeutic tool in cancer treatment.

The authors present insights into several areas of microRNA cancer research that requires further investigation in the near future, including: the impact of expression variation of several components of the microRNA biogenesis machinery, the direct role of microRNA epigenetic regulation of chromosomal DNA, and designing effective and safe microRNA drug-delivery systems. These three areas are highlighted by the authors as important steps into elucidating the total impact and use of microRNA biology in cancer development and treatment. Undoubtedly, further research in these areas will greatly enhance what is already know about microRNA regulation in cancer biology and may provide novel avenues for drug therapies.

Lujambio, A. and S.W. Lowe, The microcosmos of cancer.
Nature. 482(7385): p. 347-55.

http://www.ncbi.nlm.nih.gov/pubmed?term=the%20microcosmos%20of%20cancer

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miRviewer: A multispecies microRNA homologous viewer

Noam — Thu, 16 Feb 2012 15:56:30 +0000

In order to better understand microRNAs of interest it is of utmost importance to learn about the genomic conservation of these genes. The miRviewer web-server encompasses all known (and some novel) microRNAs of currently fully annotated animal genomes in a visual ‘birds-eye’ view representation. miRviewer provides a graphical outlook of the current microRNA world together with sequence alignments and secondary structures of each microRNA. As a test case the expression of several microRNAs in various animals were experimentally validated. Therefore miRviewer completes the homologous microRNA space with hundreds of unreported microRNAs.

miRviewer is available at: http://people.csail.mit.edu/akiezun/miRviewer

miRviewer: A multispecies microRNA homologous viewer.
Kiezun A, Artzi S, Modai S, Volk N, Isakov O, Shomron N.
BMC Res Notes. 2012 Feb 13;5(1):92. [Epub ahead of print]
PMID: 22330228 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22330228

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miRNAkey – A software pipeline for the analysis of microRNA Deep Sequencing data