Abstract

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.

Highlights

  • Hepatitis C virus (HCV) is a major public health problem with 71 million infected people worldwide [1]

  • Further studies are required to elucidate the promising therapeutic use of miR-155 inhibitor. Another analysis performed on lymphoma tissue samples, revealed 52 miRNAs differentially expressed in HCV-associated diffuse large B cell lymphoma (DLBCL) [87]

  • MiR 17-92 is a cluster of microRNAs transcribed from a polycistronic gene, comprising of 6 different mature microRNAs: miR-17, miR-18, miR-19a, miR-19b, miR-20a, and miR-92a [89] that was found overexpressed in lymphoma cell lines, and in patients with DLBCL for the first time [89,90]

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Summary

Introduction

Hepatitis C virus (HCV) is a major public health problem with 71 million infected people worldwide [1]. HCV is a hepatotropic and lymphotropic virus that can establish chronic infection, leading to hepatocellular carcinoma (HCC) and lymphoproliferative disorders (LPDs) such as mixed cryoglobulinemia (MC) and non-Hodgkin’s lymphoma (NHL). Alterations in miRNA expression patterns have been reported in human pathologies including cancer, cardiovascular and metabolic diseases, diabetes, and viral infection [6]. We will summarize some aspects of miRNAs to HCV-induced diseases, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers based on association analyses. We will provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders

MicroRNAs in the HCV Life Cycle
MicroRNAs in HCV Related HCC
MicroRNAs in HCV-Related Lymphomas and Lymphoproliferative Disorders
Cluster miR 17-92 in HCV-Related Cryoglobulinemic Vasculitis
Patients and Methods
Results
Discussion
Full Text
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