Abstract

Exosomic microRNAs Orchestrate the Biology of the Tumor Microenvironment

Muller Fabbri, Assistant Professor, University of Southern California

MicroRNAs (miRNAs) are small non-coding RNAs with gene regulatory function, whose expression is dys-regulated in all types of human cancer. MiRNAs play a central role in human carcinogenesis and specific signatures of dys-regulated miRNAs harbor diagnostic, prognostic and theranostic implications for several types of human cancers. Recent evidence suggests that miRNAs can be secreted by cancer cells within microvesicles called exosomes and can be transferred to surrounding cells within the tumor microenvironment. Once in the “recipient” cell, miRNAs can target genes both in a “traditional” way (by binding to their mRNA and preventing their translation) or through “unconventional” ways, such as binding to Toll-like receptors and triggering an inflammatory response which ultimately promotes tumor growth, dissemination and the development of drug resistance. The identification of this central role of exosomic miRNAs in the biology of the tumor microenvironment reveals previously unsuspected strategies to switch the peri-tumoral microenvironment from cancer-permissive to cancer-repressive.