Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma

Abstract

Small extracellular vesicles (exosomes) are important components of the tumor microenvironment. They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication. Exosomes transmit biological molecules obtained from parent cells, such as proteins, lipids, and nucleic acids, and are involved in cancer development. MicroRNAs (miRNAs), the most abundant contents in exosomes, are selectively packaged into exosomes to carry out their biological functions. Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis, progression, and drug resistance of hepatocellular carcinoma (HCC). In addition, exosomes have great industrial prospects in the diagnosis, treatment, and prognosis of patients with HCC. This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC. Finally, we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.

Keywords: Hepatocellular carcinoma; MicroRNA; Exosomes; Extracellular vesicles; Nonparenchymal cells

Core Tip: Hepatocellular carcinoma (HCC) is one of the most serious cancers in adults, and microRNAs (miRNAs) in small extracellular vesicles (exosomes) play a vital role in the pathological processes of HCC. Recent studies on exosomal miRNAs in HCC mainly focus on miRNA profiling but place little emphasis on where miRNAs come from and what target cells they act on. This review focused on the origin of exosomal miRNAs according to their parent cells in the tumor microenvironment and their role in HCC pathogenesis, contributing to a better understanding of exosomal miRNAs in the tumor microenvironment.