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.
Highlights
As a major adult liver malignancy, Hepatocellular carcinoma (HCC) accounts for 75-85% of all primary liver cancers with easy metastasis, poor prognosis and low survival rate [1]
This review, we aim to address the biology of exosomes, how exosomal non-coding RNAs (ncRNAs) contribute to the development of HCC with a major focus on their potential clinical applications in diagnosis and therapy
It has been shown that exosomal long non-coding RNAs (lncRNAs) H19 promoted the development of HCC including proliferation, invasion and migration and suppressed HCC cells apoptosis treated with propofol through upregulating LIM domain kinase 1 (LIMK1) via sponging miR-520a-3p [100]
Summary
As a major adult liver malignancy, Hepatocellular carcinoma (HCC) accounts for 75-85% of all primary liver cancers with easy metastasis, poor prognosis and low survival rate [1]. In the past few years, accumulating evidence has demonstrated the regulatory roles of diverse categories of non-coding RNAs (ncRNAs) in liver carcinogenesis associated with many etiologies, including HBV, HCV and NAFLD. As a result, when diagnosed, most patients with HCC are at an advanced stage They usually accompany with multiple intrahepatic or distant metastasis and miss the opportunity of radical treatments such as surgical resection or orthotopic liver transplantation. Exosomes are distributed in the majority of body fluids, including blood, urine, breast milk, saliva, tears, cerebrospinal fluid, bronchial lavage fluid, amniotic fluid and synovial fluid [21–23] These nanostructures usually contain proteins, lipid molecules, nucleic acids and other inorganic substances such as Ca2+ [16, 20]. A growing body of studies have demonstrated that exosomal ncRNAs are involved in the potential regulation of tumor metastasis, angiogenesis, immune escape, metabolic reprogramming and drug resistance.
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