Arresting the Culprit: Targeted Antagomir Delivery to Sequester Oncogenic miR-221 in HCC

Abstract

Various treatment options are available for hepatocellular carcinoma (HCC); however, the overwhelming majority of them fail to extend patient survival, especially in cases of advanced disease. Although a number of different genetic lesions have been linked to HCC, the expression of oncogenic microRNAs (miRNAs), such as miR-221 and miR-222, are consistently found elevated in HCC tumor specimens,1,2 suggesting that silencing of these miRNAs might slow or stop tumor growth. In a recent study, Park et al. show that systemic administration of a chemically modified oligonucleotide that binds to and sequesters miR-221 is efficacious in HCC.3 Their approach identified a preferred chemical modification on the oligonucleotide that allowed its accumulation in hepatocytes, which led to therapeutic silencing of miR-221, reduced cellular proliferation, and most importantly increased survival of an orthotopic mouse model of HCC. Although this approach has yet to be tried in human patients, it appears likely that treatments involving miRNA overexpression or silencing, such as these, will translate efficiently.