Abstract
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.
Highlights
KOŁAT et al: EXOSOMES AS CARRIERS Long non‐coding RNAs (lncRNAs) externalization of transferrin receptors into the intercellular space during sheep reticulocyte maturation [1]
Exosome secretions and their molecular mechanisms are rather obscure, since their release is regulated by several signal molecules and various processes including ceramide synthesis and Ca2+signalling [3]
The biogenesis follows the following sequence: the process begins with membrane invagination and exosome release to cytoplasm, followed by early endosome (EE) formation, and the formation of intraluminal vesicles (ILVs) inside the late endosome (LE)
Summary
As a result of maintaining full stability of lncRNA in extracellular vesicles as mentioned earlier, these transcripts can be taken up by target cells with their full functionality preserved [78]. There are potential approaches to inducing overexpression of lncRNA MEG3 (Maternally Expressed Gene 3) in lung adenocarcinoma in order to increase sensitivity to cisplatin‐based chemotherapy [82] Another potential type of lncRNA‐based therapy exploits the ‘sponge’ activity of those transcripts, resulting in lowered miRNA activity in tumours [81]. Investigation of new tools using the epigenetic functionality of lncRNAs could help in the research and treatment of diseases that depend on epigenetics [83] When it comes to the development of exosomal lncRNA‐based therapeutics, a few problems were identified including uncertain functionality in biological pathways, the pharmacokinetics and toxicity of lncRNAs and the precise quantification of EV‐bounded non‐coding transcripts which need to be addressed [84]. There are still several challenges that needs to be tackled in order to provide efficient EV‐based lncRNAs therapeutics for clinical application, but the current state of research offers promise
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