The microRNAs Europe Meeting is perhaps one of the best-kept secrets in the non coding RNA community. Similar to those indie music festivals where sometimes you have the opportunity to meet face to face first-line rock stars, microRNA Europe has had among its speakers first-line scientific stars such as Craig Mello, Elizabeth Blackburn or Jack Szostak talking for an audience not bigger than 100 people.
Even the venue where the meetings are held would attract scientists from around the globe: the impressive Peterhouse is the oldest College of the University of Cambridge and still a hub for scientific innovation, see this earlier Epigenie post for details.
This year’s microRNAs Europe 2014 meeting (3-4 November) was held together with the 3rd Single Molecule Biology, Genome Engineering and Editing Europe Meeting at the Peterhouse. This mix was an excellent choice from the organizers given the broad applicability genome editing techniques are gaining within the epigenetic field.
Keynote scientific speakers were Rene Ketting University of Mainz, Germany), Hagan Bayley (University of Oxford, UK), William Skarnes (Sanger Institute, Cambridge, UK) and Tudor Fulga (University of Oxford, UK) among other exciting speakers. Plenty of good science to listen to! Check the meeting’s full program at http://www.expressgenes.com/micrornai2014/main.html.
Priming the next generation with small RNAs
René F. Ketting, University of Mainz, Germany
The lecture focused on piRNAs and their role in stabilizing the genome by repressing transposons. This repression is restricted to the germline and passed to the next generation in an epigenetically determined mechanism suggesting that piRNAs and other small RNAs are involved in the establishment of transgenerational memory. Based on observations made in his lab, Dr. Ketting showed that small RNAs are used to transmit information form one generation to the other.
Epigenetic factors involved in the (osteoblast) mineralizing/demineralizing capability of cell phenotypes: Histone deacetylases, transcription factors, microRNAs and vitamin K2
Jan Ohholm Gordeladze, University of Oslo, Norway
The lecture focused on the adaptation of osteoblast phenotype by complex regulatory loops engaging transcription factors (SP1, SP3, ETS1) and microRNAS (miR-23, 27, 29, 133, 149, 204, 211, 328), whose expressions are regulated by histone modification mediated by HDACs, including Sirtuins. This complex interplay is affected in osteoblast by signaling pathways activated by vitamin K2, driving osteoblast phenotypic development. Dr. Gordeladze brought up for the first time a question that came back several times during the meeting: Do individual microRNA act on their own or is microRNA action coordinated? He proposed that epigenetic regulation may be crucial in answering this question. Two later lectures from Jennifer Winter (University of Mainz, Germany) and Carlos P. Fitzsimons (University of Amsterdam, the Netherlands) addressed this point bringing up the concept of microRNA cooperativity.
Lin28A regulates neuronal differentiation and controls miR-9 production
Gracyan Michelewski, University of Edinburg, UK
The lecture focused on the very interesting concept of post-transcriptional regulation of microRNA expression. MicroRNAs shape and establish neural stem cell fate and state transitions by acting on specific targets. Therefore, microRNA expression is tightly regulated at the transcriptional level. Dr. Michelewski showed that a subset of microRNAs crucial for neuronal differentiation are also regulated post-transcriptionally by the action of the RNA-binding protein Lin28A, inducing miR precursor degradation. This mechanism was exemplified by the regulation of miR-9 by Lin28A, showing that Lin28A is key for the regulation of neuronal differentiation of P19 stem cells.
Deciphering function and regulation of miRNA in neural differentiation in the developing cerebral cortex
Li Zeng, National Neuroscience Institute, Singapore
The lecture focused on the regulation of neural stem cell proliferation and differentiation during cortical development. Dr. Zeng showed that this is achieved, at least in part, by microRNA-mediated regulation of PCM1 expression, a gene that may be associated with autism spectrum disorders.
mir-7: a potent tumor suppressor and candidate for replacement therapy
Peter Leedman, QEII Medical Centre, Nedlands, Australia
The lectured focused on the role of miR-7 as tumor suppressor in, among others, liver cancer. Mir-7 functions to coordinately dictate the expression of direct targets such as EGFR, IGF1, Raf1 and IRS-2, which impact on the activity of the AKT/Stat3 pathway, decreasing tumor growth. Dr. Leedman discussed his lab’s current efforts to take miR-7 towards a microRNA replacement therapy for cancer.
Deregulation of miR-139-3p and miR-199a-3p drives leukemic transformation of inter-strand cross-link induced bone marrow failure
Stefan Erkeland, Erasmus University Medical Center, Netherlands
The lecture focused on mechanisms of leukemic transformation associated with Fanconi Anemia. Dr. Erkeland showed that the coordinated action of two microRNAs, miR-139-3p and miR-199a-3p, regulates the expression of targets such as RUNX1 and SUZ12, implicated in leukemic transformation. microRNA-mediated control of specific targets in hematopoietic stem and progenitor cells seems to be crucial in leukemic transformation associated with Fanconi Anemia and miR-139-3p and miR-199a-3p may represent potential therapeutic targets.
Deciphering miRNA-terget regulation by site-specific genome engineering.
Tudor A. Fulga, University of Oxford, UK
The lecture focused on the description of a new method to validate microRNA binding elements using the TALEN and CRISPR/Cas9 systems. Using this systems Dr. Fulga discussed interesting observation indicating that miRNA:target stoichiometry is crucial for microRNA activity, and that not all microRNA binding elements are functional in their original context, even when they have been validated by other luciferase reporters and other commonly used techniques.
Early diagnosis of lung cancer and mesothelioma by microRNA. Where are we?
Oluf Dimitri Roe, Norwegian University of Science and Technology, Norway
The lecture focused on the potential use of microRNAs as biomarkers of lung cancer. Several groups have tried to identify individual microRNAs in serum of patients at risk of lung cancer to use them as biomarkers, but none has been found to be robust enough, yet. Dr. Roe discussed his lab’s effort to use microRNAs, proteomics ad metabolomics combined in serum drawn from patients 3-5 prior to the cancer diagnose and characterize “signatures” of potential clinical value.
miR-379-410 cluster regulation in neurogenesis and neuronal migration
Jennifer Winter, University of Mainz, Germany
The lecture focused on the role of the genomic microRNA cluster miR-379-410 in the regulation of neurogenesis during embryonic development. Dr. Winter showed that three of the microRNAs transcribed from this cluster cooperatively regulate the expression of the cell adhesion molecule N-cadherin, thus affecting neurogenesis and neuronal migration in the developing cerebral cortex. This 3-some cooperativity may extend to other biologically relevant targets, underscoring the relevance of understanding and considering cooperativity as a key feature of microRNA coordinated actions.
Cardiac immune activation in heart failure. A causative role for the proinflammatory miR-155.
Blanche Schroen, Maastricht University, Netherlands
The lecture focused on the role of Immune activation as possible therapeutic target in heart failure. Dr. Schroen showed that miR-155 functions selectively in cardiac monocytes/macrophages to impact inflammation and function, resulting in protection from cardiac tissue remodeling after hart failure and suggested that miR-155 could be a future therapeutic target.
This is just a brief highlight of some of the excellent 36 talks that followed one another last week in Cambridge, UK, giving the audience no rest in scientific excitement. As next year will be microRNAs Europe Meeting 10th anniversary, we can expect for sure another exciting lineup, so block you calendar for November 2-3, 2015 and come to this exciting meet-and-greet conference.
**Thanks to Carlos P. Fitzsimons from the University of Amsterdam, the Netherlands for providing this event coverage.