Exosomal non-coding RNAs: a promising cancer biomarker

Abstract

Novel and non-invasive biomarkers are urgently needed for early detection of cancer. Exosomes are nano-sized particles released by cells and contain various bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. Increasing evidence suggests that exosomes play critical roles in tumorigenesis, tumor growth, metastasis, and therapy resistance. Exosomes could be readily accessible in nearly all the body fluids. The altered production of exosomes and aberrant expression of exosomal contents could reflect the pathological state of the body, indicating that exosomes and exosomal contents can be utilized as novel cancer biomarkers. Herein, we review the basic properties of exosomes, the functional roles of exosomes in cancer, and the methods of detecting exosomes and exosomal contents. In particular, we highlight the clinical values of exosomal non-coding RNAs in cancer diagnosis and prognosis.

Exosomal miRNAs as novel cancer biomarkers: Challenges and opportunities

“…Moreover, it has been discovered that tumor repressor protein p53 and its downstream effector TSAP6, could increase the exosome production (Yu, Harris, & Levine, ). As mentioned above, during the formation of exosomes, they receive the components of originating cell, thus based on their sources, exosomes carry the various types of molecules, such as miRNA, mRNA, DNA, long non‐coding RNA (LncRNA), proteins, and lipids (Yang, Fu, ). ExoCarta (http://www.exocarta.org) (Simpson et al, ), Vesiclepedia (http://www.microvesicles.org) (Kalra et al, ), and EVpedia (http://www.evpedia.info) (Kim et al, ), are three online databases, presenting the latest contents of EVs to investigators.…”

“…For instance, the membrane of exosomes is enriched with high levels of cholesterol, ceramide, sphingomyelin and glycerophospholipids, with long and saturated fatty‐acyl chains (Subra, Laulagnier, Perret, & Record, ; Trajkovic et al, ). Furthermore, exosomes contains a set of different proteins, including heat shock proteins (HSP60, HSP70, HSP90), cytoskeletal proteins (Myosin, β‐actin, tubulin), MVB synthesis proteins (Alix and Tsg101), Integrins and tetraspanin family proteins (CD9, CD63, CD81), membrane transporters, fusion proteins (Annexins, Rab GTPases, flotillins) and glycolytic proteins (Enolase 1 or ENO1 and Glyceraldehyde 3‐phosphate dehydrogenase or GAPDH) (Raposo & Stoorvogel, ; Yang, Fu, ) (Figure ). Interestingly, exosomes also carry some proteins, involved in specific cellular functions for example, epithelial cell adhesion molecule (EpCAM), abundant in exosomes, derived from epithelial tumor cell (Runz et al, ), antigen presenting cell‐derived exosomes, express MHC class II on their surface (Théry, Zitvogel, & Amigorena, ), mature dendritic cells secrete exosomes, containing intercellular adhesion molecule 1 (ICAM1) (Nolte‐'t Hoen, Buschow, Anderton, Stoorvogel, & Wauben, ; Segura, Guerin, Hogg, Amigorena & Thery, ).…”

“…Cancer is one of the important causes of death worldwide (Mathers, ). Therefore, early detection of cancer is vital for increasing survival and effective patient management (Schwarzenbach, ; Yang, Fu, Xu, & Zhang, ). Tumor biopsy is an invasive technique that is commonly used for diagnosis of cancers.…”

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

“…Then, all other species of RNAs were identified in exosomes including transfer RNAs (tRNAs), long noncoding RNAs (lncRNAs), and viral RNAs (Tran, 2016). LncRNAs, more than 200 nucleotides in length, are involved in regulating gene expression at both genetic and epigenetic levels (H. Yang et al, 2016 Kahlert et al, 2014;Kalluri, 2016). Exosomal DNA represents the whole genome and shares the same mutational status with parental cancer cells (Thakur et al, 2014).…”

Biomarkers, inflammation and cancer: where to go?

“…Because of relatively low sensitivity and specificity of these protein biomarkers, the search for new biomarkers is ongoing. Yang et al [7] present a review on exosomal RNAs as a biomarker in cancer. As exosomes play an important role in the pathogenesis of cancer, it is not surprising that the concentrations of exosomal noncoding RNAs such as microRNAs, long non-coding RNAs, and circular RNAs are increased in patients across of spectrum of malignancies.…”