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

Table 1 MicroRNAs with a role in hepatocellular carcinoma

miRNAs	Function	Outcomes
miR-22	Predicted to bind iron-bound transferrin receptor (TfR1)	Targets TfR1, DMT1 expression thereby inhibiting cell cycle progression and growth
miR-200a
miR-320
miR-200b	Targets ferritin heteropolymers (FtH1, FtL)	Decreased miR-200b linked with enhanced cancer aggressiveness via increased iron indices
miR-122	Targets HFE, hemojuvelin, BMPr1a, BMP/SMAD signalling, hepcidin	Control of systemic iron homeostasis. Decreased miR-122 corresponds to decreased HFE and hemojuvelin expression. This correlates with increased hepcidin expression

HCC: Hepatocellular carcinoma; miR/miRNA: MicroRNA; DMT: Divalent metal transporter; HFE: Human haemochromatosis; BMP: Bone morphogenetic protein; FtH: Ferritin heavy; FtL: Ferritin light.

Table 2 MicroRNAs as potential diagnostics and therapeutics for hepatocellular carcinoma

miRNAs	Detail	Relevance
miR-221	4.8 fold higher in HCC patients, positively correlates with cirrhosis, tumour size and stage. Negatively correlates with overall survival	Potential circulating biomarker
miR-199a	Reduced and significantly associated with HCC	Potential circulating biomarker
miR-16	Reduced and significantly associated with HCC	Potential circulating biomarker
miR-26	Low levels associated with high IL-6 and shorter survival	Potential biomarker to assess prognosis of HCC
miR-375	Lower than normal levels associated with β-catenin mutation	Potential for HCC classification system, determine treatment allocation
miR-107	Reduced levels associated with HFN 1α	Potential for HCC classification system, use to determine treatment allocation
miR-122	Expression inhibited using Miravirsen LNA-modified oligonucleotides	Direct effect in chimpanzee model in reducing HCV replication and viraemia
miR-196	Selective target for intervention	Implications for treatment
miR-26a	Deliverable to HCC sites using adeno-associated virus serotype 8	Decreased proliferation and induced tumour-specific apoptosis
miR-124	Induces tumour-specific apoptosis	Prevents and suppresses HCV development in murine model

HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; miR/miRNA: MicroRNA; IL: Interleukin.