The Potential Roles of Exosomal Non-Coding RNAs in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the sixth highest-incidence cancer and the 4th most deadly cancer all over the world, with a high fatality and low diagnostic rate. Nowadays, Excessive alcohol consumption, type-2 diabetes, smoking and obesity have become some primary risk factors of HCC. As intercellular messenger transporting information cargoes between cells, exosomes are a type of extracellular vesicles (EVs) released by most types of cells including tumor cells and non-tumor cells and play a pivotal role in establishing an HCC microenvironment. Exosomes, and more generally EVs, contain different molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids and transcription factors. The three main ncRNAs in exosomes are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs). NcRNAs, identified as essential components, are selectively sorted into exosomes and exosomal ncRNAs show great potential in regulating tumor development, including proliferation, invasion, angiogenesis, metastasis, immune escape and drug resistance. Here, we chiefly review the formation and uptake of exosomes, classification of exosomal ncRNAs and current research on the roles of exosomal ncRNAs in HCC progression. We also explored their clinical applications as new diagnostic biomarkers and therapeutic avenues in HCC.

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

“…lncRNAs work mainly through the following four ways: first, induction, lncRNAs can bind to a specific miRNA, which can indirectly regulate the target gene; second, lncRNAs can act as a signal molecule on the pathway and regulate the upstream- and downstream-related genes of its target gene [ 31 , 32 ]. Third, by guiding the relevant RNA-binding proteins, lncRNAs are able to mediate the target genes via cis- or trans-regulation to specific protein complex sites [ 33 , 34 ]. Fourth, scaffolds, lncRNAs can be used as a platform; on this platform, a variety of related molecular complexes can be combined together to enhance the information transmission and interaction between molecular complexes [ 35 , 36 ].…”

Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

“…Hepatocellular carcinoma causes approximately 600,000 deaths each year. It is the sixth most common cancer all over the world and the third leading cause of cancer-related death [ 61 , 62 ]. Chronic hepatitis B or C virus infections are the pivotal development factors of hepatocellular carcinoma [ 63 ].…”

Exosomal MiRNAs in Osteosarcoma: Biogenesis and Biological Functions

“…Third, it could offer real-time information and thus reflect the tumor cell evolution ( Panvongsa et al, 2022 ). Fourth, miRNAs inside the exosome are more stable since the phospholipid bilayer membrane of exosomes can protect miRNAs from the degradation by RNase ( Wang et al, 2022 ). Thus, exosomal miRNA-based biomarkers in liquid biopsies may open up novel possibilities for cancer screening, early diagnosis, and monitoring ( Panvongsa et al, 2022 ).…”

“…Exosomes could be released by a variety of types of cells and convey bioactive cargoes to modulate crosstalk between donor and recipient cells. MiRNAs are selectively sorted into exosomes as one of the essential components ( Wang et al, 2022 ). As aforementioned, various carcinogenesis-associated exosomal miRNAs are aberrantly expressed in osteosarcoma, and are proven to be markedly correlated with its onset and progression.…”