Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells.

Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular Vesicles and the Society for Clinical Research and Translation of Extracellular Vesicles Singapore convened a Workshop on this topic to discuss the opportunities and challenges associated with development of EV-based therapeutics at the preclinical and clinical levels. This review outlines topic-specific action items that, if addressed, will enhance the development of best-practice models for EV therapies.

Mesenchymal stem cell (MSC), a widely used adult stem cell candidate for regenerative medicine, has been shown to exert some of its therapeutic effects through the secretion of extracellular vesicles (EVs). These homogenously sized EVs of 100–150 ηm exhibited many exosome‐like biophysical and biochemical properties and carry both proteins and RNAs. Recently, exosome‐associated proteins in this MSC EV preparation were found to segregate primarily to those EVs that bind cholera toxin B chain (CTB), a GM1 ganglioside‐specific ligand, and pulse‐chase experiments demonstrated that these EVs have endosomal origin and carried many of the exosome‐associated markers. Here, we report that only a fraction of the MSC EV proteome was found in CTB‐bound EVs. Using Annexin V (AV) and Shiga toxin B subunit (ST) with affinities for phosphatidylserine and globotriaosylceramide, respectively, AV‐ and a ST‐binding EV were identified. CTB‐, AV‐ and ST–binding EVs all carried actin. However, the AV‐binding EVs carried low or undetectable levels of the exosome‐associated proteins. Only the ST‐binding EVs carried RNA and EDA‐containing fibronectin. Proteins in AV‐binding EVs were also different from those released by apoptotic MSCs. CTB‐ and AV‐binding activities were localized to the plasma membrane and cytoplasm of MSCs, while ST‐binding activity was localized to the nucleus. Together, this study demonstrates that cells secrete many types of EVs. Specifically, MSCs secrete at least 3 types. They can be differentially isolated based on their affinities for membrane lipid‐binding ligands. As the subcellular sites of the binding activities of these ligands and cargo load are different for each EV type, they are likely to have a different biogenesis pathway and possibly different functions.

The sensitive analysis of small lipid extracellular vesicles (EVs) by using a grating-coupled surface plasmon resonance (GC-SPR) biosensor has been reported. In order to enable the analysis of trace amounts of EVs present in complex liquid samples, the target analyte is pre-concentrated on the sensor surface by using magnetic nanoparticles and its affinity binding is probed by wavelength interrogation of SPR. The GC-SPR has been demonstrated to allow for the implementation of efficient pulling of EVs to the sensor surface by using magnetic nanoparticles and an external magnetic field gradient applied through the sensor chip. This approach overcomes slow diffusion-limited mass transfer and greatly enhances the measured sensor response. The specific detection of different EV populations secreted from mesenchymal stem cells is achieved with a SPR sensor chip modified with antibodies against the surface marker CD81 and magnetic nanoparticles binding the vesicles via annexin V and cholera toxin B chain.

Background: Since it is known that bitter taste receptors (TAS2Rs) are expressed and functionally active in various extra-oral cells, their genetic variability and functional response initiated by their activation have become of broader interest, including in the context of cancer. Methods: A systematic research was performed in PubMed and Google Scholar to identify relevant publications concerning the role of TAS2Rs in cancer. Results: While the findings on variations of TAS2R genotypes and phenotypes and their association to the risk of developing cancer are still inconclusive, gene expression analyses revealed that TAS2Rs are expressed and some of them are predominately downregulated in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, receptor-specific, agonist-mediated activation induced various anti-cancer effects, such as decreased cell proliferation, migration, and invasion, as well as increased apoptosis. Furthermore, the overexpression of TAS2Rs resulted in a decreased tumour incidence in an in vivo study and TAS2R activation could even enhance the therapeutic effect of chemotherapeutics in vitro. Finally, higher expression levels of TAS2Rs in primary cancerous cells and tissues were associated with an improved prognosis in humans. Conclusion: Since current evidence demonstrates a functional role of TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics.