Exosomal microRNAs as a potential therapeutic strategy in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second cause of cancer-related death worldwide. The incidence of HCC is constantly increasing in correlation with the rise in diabetes and obesity, arguing for an urgent need for new developments in the treatment of this lethal cancer. Exosomes are small double-membrane vesicles loaded with distinct cargos, particularly small non-coding RNAs called microRNAs, representative of each donor cell and secreted to affect the features of neighboring cells or recipient cells located further away, like in the case of metastasis. A better understanding of the role of exosomes with a microRNA signature in cancer pathogenesis gave rise to the concept of their use as a non-invasive diagnostic biomarker and in the treatment of cancer, including HCC. In this communication, we review recent works that demonstrate that hepatic stellate cells establish an epigenetic communication with liver cancer cells, which affects their pro-malignant features. If naturally secreted patient-derived exosomes show major limitations concerning their clinical use, bio-engineered exosome mimetics that incorporate controlled components and exhibit no protumoral properties could be promising carriers for the treatment of liver cancers, which is the organ preferentially targeted by systemic injection of exosomes.

Keywords: MicroRNAs, Hepatocellular carcinoma, Targeted therapy, Exosomes

Core tip: Despite the intensive research efforts to identify the molecular events responsible for the emergence of liver cancer, hepatocellular carcinoma (HCC) remains a major health problem worldwide. Thus, the identification of new therapeutic opportunities to counteract the challenging issues linked to HCC heterogeneity and resistance to conventional treatments is a short-term necessity. Over the last few decades, microRNAs have appeared as interesting therapeutic strategies with their pleiotropic inhibitory action, but the use of a delivery system is a requirement for miRNA mimic administration. Exosomes, which are small vesicles naturally produced by immune cells and aberrantly by cancer cells, have recently emerged as a promising vehicle.