Abstract
Exosomes are secreted by different types of cells in tumor microenvironment (TME) and participate in multiple biological processes of tumors. Non-coding RNAs (ncRNAs) enveloped in exosomes and released to the TME are shown to be involved in tumorigenesis and development, as well as act as important intracellular communication mediators. However, the understanding on the exact regulatory functions and substrates of exosomal RNA is still at an early stage. In this review, we provided an overview on recent studies on exosomes mediating the modulation of both tumor cells and immune cells, then summarized the exosomal ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)] secreted by tumor cells and stromal cells that exhibited potential capabilities to regulate tumor cell growth, progression, metastasis, drug resistance, and immune response. Our review may hopefully inspire a deeper understanding on the ncRNAs’ function as useful biomarkers for the diagnosis, prognosis, and as novel targets therapy for cancer.
Highlights
The tumor microenvironment (TME) is a complex ecosystem formed by cells of diverse types, including endothelial, fibroblastic, and immune cells, which participate in all stages of tumor initiation and progression (Meurette and Mehlen, 2018; Li and Nabet, 2019)
We provided an overview on recent studies on exosomes mediating the modulation of both tumor cells and immune cells, summarized the exosomal ncRNAs [such as microRNAs, long non-coding RNAs, and circular RNAs] secreted by tumor cells and stromal cells that exhibited potential capabilities to regulate tumor cell growth, progression, metastasis, drug resistance, and immune response
Studies reveal that circPRMT5 in the serum and urine exosomes of urothelial carcinoma of the bladder tissue enhances the epithelial–mesenchymal transition (EMT) process via sponging miR-30c through the SNAIL1/E-cadherin pathway (Chen X. et al, 2018), whereas circ-PDE8A from livermetastatic pancreatic ductal adenocarcinoma (PDAC) cells acts as a ceRNA of miR-338 to upregulate MACC1 and MET to increase the invasive growth of PDAC cells, thereby affecting tumor progression and metastasis (Li Z. et al, 2018)
Summary
The tumor microenvironment (TME) is a complex ecosystem formed by cells of diverse types, including endothelial, fibroblastic, and immune cells, which participate in all stages of tumor initiation and progression (Meurette and Mehlen, 2018; Li and Nabet, 2019). This chapter focused on the different types of exosomal ncRNAs (including miRNA, lncRNA, and circRNA)-based regulation in the microenvironment modulation through different mechanisms, including energy metabolism regulation, protumor signal transportation, and inhibitory factor blockage, resulting in tumor cell growth and survival, inducing angiogenesis, and enhancing ECM remodeling and EMT process, thereby contributing to tumor invasion and metastasis (Figure 3 and Table 1).
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