Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications

Abstract

Gliomas are complex and heterogeneous brain tumors with poor prognosis. Glioma cells can communicate with their surroundings to create a tumor-permissive microenvironment. Exosomes represent a new means of intercellular communication by delivering various bioactive molecules, including proteins, lipids and nucleic acids, and participate in tumor initiation and progression. Noncoding RNAs (ncRNAs) including microRNA, long-noncoding RNA, and circular RNA, account for a large portion of human transcriptome and play important roles in various pathophysiological processes, especially in cancers. In addition, ncRNAs can be selectively packaged, secreted and transferred between cells in exosomes and modulate numerous hallmarks of glioma, such as proliferation, invasion, angiogenesis, immune-escape, and treatment resistance. Hence, the strategies of specifically targeting exosomal ncRNAs could be attractive therapeutic options. Exosomes are able to cross the blood brain barrier (BBB), and are readily accessible in nearly all types of human biofluids, which make them the promising biomarkers for gliomas. Additionally, given the biocompatibility of exosomes, they can be engineered to deliver therapeutic factors, such as RNA, proteins and drugs, to target cells for therapeutic applications. Here, we reviewed current research on the roles of exosomal ncRNAs in glioma progression. We also discussed their potential clinical applications as novel biomarkers and therapeutics.

Keywords: Cancer diagnosis; Cancer therapy; Exosome; Extracellular vesicles; Glioma; Noncoding RNA.

Fig. 1

Roles of exosomes in glioma. a exosomes participate in cell-to-cell communication by delivering various bioactive molecules, including proteins, lipids and nucleic acids, in the tumor microenvironment. b exosomes serve as promising biomarkers. c exosomes have novel therapeutic applications

Fig. 2

The main process of exosome biogenesis and release. a The biogenesis of exosome begins at endosome formation through endocytosis at the plasma membrane, and then early endosomes maturate to multivesicular bodies (MVB). Exosomes are formed as intraluminal vesicles (ILV) in MVBs though endosomal sorting complexes required for transport (ESCRT) dependent or independent pathway. Generally, MVBs either fuse with the lysosome for degradation or fuse with the plasma membrane, which results in ILVs (exosomes) secretion. After secretion, exosomes uptake by target cells is mediated by endocytosis, fusion with the plasma membrane or ligand/receptor interaction. b Both the ESCRT- dependent and independent pathway are implicated in controlling the cargos sorting of exosomes

Fig. 3

The biogenesis (a) and potential functions (b) of miRNA, lncRNA and circRNA

Fig. 4

Exosomal ncRNAs play important roles in regulating glioma proliferation/invasion (a), angiogenesis (b), immune-escape (c), and treatment resistance (d)