Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network De-regulation

Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miR, resulted in significant de-repression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis and necrosis was noted in anti-miR-21 treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21

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Wagenaar TR, Zabludoff S, Ahn SM, Allerson C, Arlt H, Baffa R, Cao H, Davis S, Garcia-Echeverria C, Gaur R, Huang SM, Jiang L, Kim D, Metz-Weidmann C, Pavlicek A, Pollard J, Reeves J, Rocnik JL, Scheidler S, Shi C, Sun F, Tolstykh T, Weber W, Winter C, Yu E, Yu Q, Zheng G, Wiederschain D