The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma.

Eva Costanzi,Cinzia Brenna,Luca Maria Neri,Gabriele Varano,Ilaria Conti,Carolina Simioni

doi:10.3390/genes12060902

Abstract

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

Highlights

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA
This review summarizes the current knowledge of EV RNA content, with a specific focus on their ability of mediating the communication between normal and pathological liver cells
The results show a high correlation of serum-circulating miRNAs and serum EV-associated miR-221, miR-222, and miR-224 in the hepatocellular carcinoma (HCC) and liver cirrhosis (LC) groups; the differences detected in serum miRNA levels were lower than those detected inside the EVs

Summary

Introduction

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). NcRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from. Extracellular vesicles (EVs)are defined as lipid bilayer particles naturally released from cells into the extracellular space. They became attractive in the research field when their potential role in cellular crosstalk was discovered [1]

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