Multiple Roles of Exosomal Long Noncoding RNAs in Cancers

Abstract

Long noncoding RNAs (lncRNAs) are not transcriptional noise, as previously understood, but are currently considered to be multifunctional. Exosomes are derived from the internal multivesicular compartment and are extracellular vesicles (EVs) with diameters of 30-100 nm. Exosomes play significant roles in the intercellular exchange of information and material. Exosomal lncRNAs may be promising biomarkers for cancer diagnosis and potential targets for cancer therapies, since they are increasingly understood to be involved in tumorigenesis, tumor angiogenesis, and chemoresistance. This review mainly focuses on the roles of emerging exosomal lncRNAs in cancer. In addition, the biogenesis of exosomes, the functions of lncRNAs, and the mechanisms of lncRNAs in exosome-mediated cell-cell communication are also summarized.

Figure 1

Functions of lncRNA. Decoys: lncRNAs act as decoys to attract transcription factors and influence protein expression [23]. Scaffolds: LncRNAs regulate gene expression by recruiting chromatin modifiers to special genomic locations acting as miRNA sponges [9, 10]. Sponge: lncRNAs can interact with miRNA, acting as “sponges” [13]. Signal: lncRNAs have a role in signal regulation [26]. Encode: lncRNAs encode functional micropeptides encoded by short open reading frames [27, 28].

Figure 2

Exosome biogenesis and exosome-mediated delivery of ncRNAs to the recipient cell [37]. A. ncRNAs bind to packing proteins and are selectively secreted. B. Early endosomes are generated from inward budding of the plasma membrane and mature after interacting with Golgi complexes. C. Late endosomes form intraluminal vesicles (ILVs) and incorporate nucleic acids. D. MVB containing ILVs then fuse with the plasma membrane and release exosomes. E. ncRNAs are transferred within exosomes to recipient cells and affect functions.