MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

Abstract

Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes.

Keywords: MicroRNAs; Liver cancer; Iron regulation; Hepatitis C; Therapeutic targets

Core tip: Hepatocellular carcinoma (HCC) has a high incidence and low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs) are regulatory RNAs that modulate protein synthesis and are involved in several biological and pathological processes including the development and progression of HCC. miRNAs represent important new targets for therapeutic intervention for HCC and have potential as diagnostic and prognostic HCC biomarkers. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes.