Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer

Exosomes are a subset of membrane-bound extracellular vesicles with diameters ranging from 30 to 100 nm. Exosomes enclose a variety of molecules, such as lipids, proteins, and non-coding RNAs. In the past decades, microRNAs (miRNAs) have attracted great attention in cancer research, as they play an important role in the occurrence and development of cancer. Increasing evidence indicates that tumor cells communicate with not only other tumor cells but also cells present in the tumor microenvironment via secretion and transfer of exosomal miRNAs. More importantly, exosomal miRNAs are found to serve as signaling molecules to regulate tumor growth, angiogenesis, metastasis, sensitivity to chemotherapy, and immune evasion. Deregulated expression of exosomal miRNAs is an early event in carcinogenesis and may reflect the malignant characteristics of cancer. Owing to the wide existence and high stability of exosomal miRNAs in body fluids, they may represent a novel class of non-invasive biomarkers for cancer. Qingdao University researchers highlight the recent advances on the functional role of exosomal miRNAs in cancer pathogenesis. They also discuss the potential clinical utility of exosome-shuttled miRNAs as biomarkers for the diagnosis and treatment of cancer.

Summary of the Function of Exosomal miRNAs in Cancer

Exosomal miRNAs play multifaceted roles in tumor initiation and development. Tumor cells could transfer exosomal miRNAs to surrounding tumor cells. In recipient tumor cells, exosomal miRNAs can control cell proliferation, invasion, and metastasis by orchestrating their downstream targets. Exosomal miRNAs mediate a special communication between tumor cells and endothelial cells, thus playing an important role in tumor angiogenesis. Drug-resistant tumor cells can transmit the resistant phenotype to drug-sensitive tumor cells through the horizontal transfer of exosomal miRNAs. In terms of mechanism, exosomal miRNAs mainly control the apoptotic or autophagic pathways, hence conferring chemoresistance to recipient tumor cells. Exosomal miRNAs serve as key messengers for exchanging information between tumor cells and immune cells (macrophages, T cells, and dendritic cells), contributing to the formation of a tumor-promoting, immunosuppressive microenvironment. In addition, exosomal miRNAs are instrumental for the cross-talk between tumor cells and CAFs within the tumor microenvironment. Tumor-derived exosomal miRNAs are capable of reprogramming and activating CAFs, thus facilitating tumorigenesis and tumor development. Exosomal miRNAs derived from adjacent CAFs in turn modulate the malignant phenotype of tumor cells.