Abstract

Hepatotropic viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major etiological agents associated with development of hepatocellular carcinoma (HCC). Progression of HCC is a multistep process that requires sequential or parallel deregulation of oncogenic and tumor suppressive pathways leading to chromosomal instability and neoplastic phenotype. In the recent years, microRNAs (miRNAs) have carved their own niche alongside oncogenes and tumor suppressors, owing to their innate ability to receive and relay multiple signals. Not surprisingly, miRNAs are fast emerging as central player in myriads of malignancies including HCC. miRNAs are reported to participate in initiation and progression of HCC, and have also been clinically correlated with risk assessment, disease grade, aggressiveness, and prognosis. Despite extensive data available on the role of miRNAs in HCC, there is a pressing need to integrate and evaluate these datasets to find its correlation, if any, with causal agents in order to devise novel interventional modalities. Through this review, we attempt to bridge the gap by consolidating the current knowledge and concepts in the field of HCC-related miRNAs with special emphasis on HBV and HCV. Further, we assess the potential of common as well as unique signatures that may be useful in developing novel biomarkers and therapeutics.

Highlights

  • According to a WHO estimate, hepatitis B virus (HBV) and hepatitis C virus (HCV) together account for ~78% of hepatocellular carcinoma (HCC) incidence worldwide and are the second leading cause of cancer mortality [1]

  • High morbidity observed in HCC is majorly attributed to lack of early detection markers and poor prognosis, which limit the options for chemotherapy, adjuvant therapies, or surgical procedures [2]

  • Non-human primates chronically infected with HCV when treated with locked nucleic acid (LNA) specific for miR-122, exhibited long-term suppression of HCV viral load, supporting therapeutic use of miRNA in HCC [2]

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Summary

Introduction

According to a WHO estimate, hepatitis B virus (HBV) and hepatitis C virus (HCV) together account for ~78% of hepatocellular carcinoma (HCC) incidence worldwide and are the second leading cause of cancer mortality [1]. Since c-Myc itself is a target of certain miRNAs, the transcriptional control of its regulators sets on a positive feedback loop for c-Myc expression in HCC [8, 11]. HBV positively regulates miR-181a transcription – an index of poor survival whereas it negatively regulates tumor suppressors, WIF1 and DKK3 (controllers of Wnt signaling pathway and miR181a targets) possibly via miR181a [15,16,17].

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