Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb 23;3(1):10.
doi: 10.3390/ncrna3010010.

Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation between Cells, Cancer Progression and Resistance to Therapies

Affiliations
Review

Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation between Cells, Cancer Progression and Resistance to Therapies

Farah Fatima et al. Noncoding RNA. .

Abstract

Extracellular vesicles (EVs) are nanosized vesicles secreted from virtually all cell types and are thought to transport proteins, lipids and nucleic acids including non-coding RNAs (ncRNAs) between cells. Since, ncRNAs are central to transcriptional regulation during developmental processes; eukaryotes might have evolved novel means of post-transcriptional regulation by trans-locating ncRNAs between cells. EV-mediated transportation of regulatory elements provides a novel source of trans-regulation between cells. In the last decade, studies were mainly focused on microRNAs; however, functions of long ncRNA (lncRNA) have been much less studied. Here, we review the regulatory roles of EV-linked ncRNAs, placing a particular focus on lncRNAs, how they can foster dictated patterns of trans-regulation in recipient cells. This refers to envisaging novel mechanisms of epigenetic regulation, cellular reprogramming and genomic instability elicited in recipient cells, ultimately permitting the generation of cancer initiating cell phenotypes, senescence and resistance to chemotherapies. Conversely, such trans-regulation may introduce RNA interference in recipient cancer cells causing the suppression of oncogenes and anti-apoptotic proteins; thus favoring tumor inhibition. Collectively, understanding these mechanisms could be of great value to EV-based RNA therapeutics achieved through gene manipulation within cancer cells, whereas the ncRNA content of EVs from cancer patients could serve as non-invasive source of diagnostic biomarkers and prognostic indicators in response to therapies.

Keywords: RNA interference; RNA-based therapeutics; biomarkers; cancer senescence; drug resistance; exRNA; extracellular vesicles; long non-coding RNAs; trans-regulation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
EV-mediated ncRNA transport and mechanism of trans-regulation, genomic instability and tumor progression. Tumor cell-derived EVs carrying ncRNAs are transported to recipient cells and may trigger cellular responses either by (a) direct receptor mediated interactions; or (b) could be endocytosed, followed by the release of ncRNAs in cytoplasm; (c) The ncRNAs may find their target mRNAs in recipient cell cytoplasm and may modulate gene expression either by repressing or activating the target genes; (d) The ncRNAs might recruit methylation machinery and may contribute to histone modifications; (e) EV-mediated delivery of splicing components may contribute to processing of precursor RNA transcripts in recipient cells and affect the transcription products; (f) The ncRNAs may target and inhibit tumor suppressor PTEN gene. These means of epigenetic regulation elicited in recipient cells consequently result into genomic instability and global changes in transcriptomic profiles ultimately giving rise to cancer initiating cell phenotypes such as epithelial mesenchymal transition. Collectively, genomic and phenotypic changes may exhibit enhanced proliferation, tumor growth, invasion and modulation of tumor microenvironment. EVs: Extracellular vesicles, ncRNAs: non-coding RNA, EMT: Epithelial mesenchymal transition.

References

    1. Nawaz M., Camussi G., Valadi H., Nazarenko I., Ekstrom K., Wang X., Principe S., Shah N., Ashraf NM., Fatima F., et al. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat. Rev. Urol. 2014;11:688–701. doi: 10.1038/nrurol.2014.301. - DOI - PubMed
    1. Kim K.M., Abdelmohsen K., Mustapic M., Kapogiannis D., Gorospe M. RNA in extracellular vesicles. Wiley Interdiscip. Rev.: RNA. 2017 doi: 10.1002/wrna.1413. - DOI - PMC - PubMed
    1. Keerthikumar S., Chisanga D., Ariyaratne D., Al Saffar H., Anand S., Zhao K., Samuel M., Pathan M., Jois M., Chilamkurti N., et al. ExoCarta: A web-based compendium of exosomal cargo. J. Mol. Biol. 2016;428:688–692. doi: 10.1016/j.jmb.2015.09.019. - DOI - PMC - PubMed
    1. Valadi H., Ekstrom K., Bossios A., Sjostrand M., Lee J.J., Lotvall J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007;9:654–659. doi: 10.1038/ncb1596. - DOI - PubMed
    1. Mathivanan S., Ji H., Simpson R.J. Exosomes: Extracellular organelles important in intercellular communication. J. Proteom. 2010;73:1907–1920. doi: 10.1016/j.jprot.2010.06.006. - DOI - PubMed

LinkOut - more resources