Abstract
Extracellular vesicles (EVs) are small membranous vesicles secreted from normal, diseased, and transformed cells in vitro and in vivo. EVs have been found to play a critical role in cell-to-cell communication by transferring non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long ncRNAs (lncRNAs) and so on. Emerging evidence shows that transferring biological information through EVs to neighboring cells in intercellular communication not only keep physiological functions, but also participate in the pathogenesis of liver diseases. Liver diseases often promote release of EVs and/or in different cargo sorting into these EVs. Either of these modifications can promote disease pathogenesis. Given this fact, EV-associated ncRNAs, such as miR-192, miR-122 and lncRNA-ROR and so on, can serve as new diagnostic biomarkers and new therapeutic targets for liver disease, because altered EV-associated ncRNAs may reflect the underlying liver disease condition. In this review, we focus on understanding the emerging role of EV-associated ncRNAs in viral hepatitis, liver fibrosis, alcoholic hepatitis (AH), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) and discuss their utility in biomarker discovery and therapeutics. A better understanding of this multifaceted pattern of communication between different type cells in liver may contribute to developing novel approaches for personalized diagnostics and therapeutics.
Highlights
Understanding the intercellular communication is rapidly becoming the new frontier in multicellular organisms
We have highlighted several of the most recent and original studies reporting the role of non-coding RNAs (ncRNAs) in extracellular vesicles (EVs) as link between liver fibrosis, viral hepatitis, non-alcoholic steatohepatitis (NASH), alcoholic hepatitis (AH) and hepatocellular carcinoma (HCC)
We found that EV-associated ncRNAs are increasingly recognized as essential regulators of biological processes in normal and pathological conditions having a high potential to targeted delivery and therapeutic intervention in liver and other diseases
Summary
Understanding the intercellular communication is rapidly becoming the new frontier in multicellular organisms. Emerging studies have identified that EVs can serve as a unique vehicle for the release of soluble and insoluble molecules and was associated with several physiological and pathophysiological processes, such as inflammation, immune modulation, neurological diseases, Extracellular Vesicles in Liver Diseases cancer and liver diseases (Cossetti et al, 2014; Hazan-Halevy et al, 2015; Polanco et al, 2016; Wong et al, 2016). Lipid and protein interactions contribute to EV uptake (Mulcahy et al, 2014) Following this discovery, we review the role of non-coding RNAs (ncRNAs) carried by EVs in diagnosis and the assessment of liver disease, and how to use them as new diagnostic biomarkers and therapeutic targets. MiRNAs were reported to target many genes and involved in regulation cell proliferation and differentiation, migration, apoptosis, and modulation of the host response to viral infection (Bartel, 2004; Salmanidis et al, 2014). Alterations in miRNAs expression profiles have been shown to be associated viral hepatitis, hepatobiliary malignancies, non-alcoholic fatty liver disease, acute liver injury from acetaminophen and liver fibrosis
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