Systemic Delivery of MicroRNA-101 Potently Inhibits Hepatocellular Carcinoma by Repressing Multiple Targets

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Human hepatocellular carcinoma (HCC) is one of the most common malignancy worldwide and among the leading causes of cancer-related death. HCC is often diagnosed at an advanced stage and there is still no effective therapeutic strategy for non-resectable HCCs. It has been suggested that the therapeutic delivery of certain miRNA(s) has a unique advantage in clinical use. We first find that the plasma levels of miR-101 are significantly down-regulated in HCC patients with distant metastasis and associated closely with HCCs progression and/or worse disease-free survival (DFS). Next, we identify that systemic delivery of lentivirus-mediated miR-101 in an orthotopic liver implanted HCC model of mouse, not only suppresses tumor xenograft growth in the liver, but also substantially blocks intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic abrogation of HCC tumorigenesis and progression in mice without toxicity. Furthermore, functional and/or mechanistic studies of miR-101 demonstrate that miR-101 in HCC cells inhibits Rho/Rac GTPase activation, and blocks HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo.

Vyšlo v časopise: Systemic Delivery of MicroRNA-101 Potently Inhibits Hepatocellular Carcinoma by Repressing Multiple Targets. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004873
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004873

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