Exosomes as carriers transporting long non-coding RNAs: Molecular characteristics and their function in cancer

摘要

Long non-coding RNAs (lncRNAs) comprise a sizeable class of non-coding RNAs with a length of over 200 base pairs. Little is known about their biological function, although over 20,000 lncRNAs have been annotated in the human genome. Through a diverse range of mechanisms, their primary function is in the regulation of the transcription of protein-coding genes. lncRNA transcriptional activation can result from a group of nucleus-retained and chromatin-associated lncRNAs, which function as scaffolds in the cis/trans recruitment of transcription factors, co-activators or chromatin remodelers, and/or promoter enhancers. Exosomes are released as extracellular vesicles and they are produced by endocytic pathways. Their synthesis is initiated by various processes including ceramide synthesis, release of intracellular Ca2+ or acid-base balance disorders. Prior to vesicle creation, selective cargo loading occurs in the Endosomal Sorting Complex Required for Transport. Participation of endosomal sorting proteins such as tetraspanins or specific sumoylated proteins required for transport has been indicated in research. The endosomal-sorting complex consists of four components, these induce the formation of multivesicular bodies and the induction of membrane deformation to form exosomes. Nanovesicles could be formed inside multivesicular bodies to allow transport outside the cell or digestion in lysosomes. The molecular content of exosomes is more heterogenic than its synthesis process, with different cargoes being examined inside vesicles with regard to the type or stage of cancers. This paper will review the importance of lncRNAs as crucial molecular content of exosomes, indicating its involvement in tumour suppression, pro-tumorigenic events and the development of novel therapeutic approaches in the near future. Further studies of their mechanisms of function are essential, as well as overcoming several challenges to gain a clearer insight to the approaches for the best clinical application.