The release of RNA‐containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA‐containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV‐RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA‐encoded messages affect signalling processes in EV‐targeted cells. Moreover, EV‐RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV‐RNA in vivo. These topics were discussed at the 2015 EV‐RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(‐RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV‐RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV‐RNA and calls for caution in interpretation of the obtained data.
MicroRNAs are short noncoding 18-25 nucleotide long RNA which bind and inhibit mRNA. Currently, there are over 1000 known human microRNAs, and microRNAs control over 50% of mammalian protein coding genes. MicroRNAs can be overexpressed or repressed in different diseases and inhibition or replacement of microRNAs is a promising area of study for therapeutics. Here we review the current knowledge of microRNA therapy, and discuss ways in which they can be utilized. We also discuss different methods of delivery of miRNA, and current clinical trials of microRNA-based therapies for disease. Finally we discuss the current limitations in the field, and how these limitations are being overcome.
A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.