Abstract
MicroRNAs (miRNAs) have generated great attention in oncology as they play a fundamental role in the regulation of gene expression and their aberrant expression is present in almost all types of tumors including pediatric ones. The discovery that miRNAs can be transported by exosomes, which are vesicles of 40–120 nm involved in cellular communication, that are produced by different cell types, and that are present in different biological fluids, has opened the possibility of using exosomal miRNAs as biomarkers. The possibility to diagnose and monitor the progression and response to drugs through molecules that can be easily isolated from biological fluids represents a particularly important aspect in the pediatric context where invasive techniques are often used. In recent years, the idea of liquid biopsy as well as studies on the possible role of exosomal miRNAs as biomarkers have developed greatly. In this review, we report an overview of all the evidences acquired in recent years on the identification of exosomal microRNAs with biomarker potential in pediatric cancers. We discuss the following herein: neuroblastoma, hepatoblastoma, sarcomas (osteosarcoma, Ewing’s sarcoma and rhabdoid tumors, and non-rhabdomyosarcoma soft tissue sarcoma), brain tumors, lymphomas, and leukemias.
Highlights
Tissue biopsy still represents the gold standard for tumor diagnosis
Sci. 2019, 20, 4600 pathway: hnRNPA2B1 recognizes the GGAG motif in 3 UTR of miRNA sequences, determining its packaging into exosomes [8]; c) the 3 end of the miRNA sequence-dependent pathway: 3 ends of uridylated endogenous miRNAs are mainly presented in exosomes derived from B cells or urine, whereas the 3 ends of adenylated endogenous miRNAs are especially presented in B cells [21]; and d) the miRNA-induced silencing complex-related pathway: the knockout of argonaute protein 2 (AGO2) could decrease the types and abundance of preferentially exported miRNAs in exosomes isolated from HEK293T cells [18]
Gene Ontology (GO) categories and pathway analyses showed that the mitogen-activated protein kinase (MAPK) and Rap1 signaling pathways, which are involved in tumor progression, were targeted by the three miRNAs upregulated in all three patients with Desmoplastic small round cell tumor (DSRCT) and that a large number of transcripts targeted by the highly dysregulated miRNAs are involved in the intracellular receptor signaling pathway and in nervous system development
Summary
Tissue biopsy still represents the gold standard for tumor diagnosis. minimally invasive approaches for detecting and monitoring tumors are needed in the pediatric setting. Liquid biopsies represent a less invasive source of biomarkers for patient monitoring and therapeutic decision. Lipids, DNA, RNA, and miRNAs that represent potential biomarkers for clinical purposes. The evidence that tumor cells communicate via the secretion of miRNAs in body fluids and that these molecules may be packed into exosomes and delivered to target cells has opened interesting scenarios for the use of these vesicles as new biomarkers. Exosomes contain specific repertoires of miRNAs, which are selectively sorted in these vesicles [8] For this reason, exosomal miRNAs display different expression patterns between cancer patients and healthy individuals. The purpose of this review is to summarize the recent supportive evidences on the potential role of exosomal miRNAs as biomarkers in pediatric cancers
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