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

• DOI: 10.1371/journal.pgen.1004873
• Publication Date: 2015-02-18T14:13:11Z
• Authors: Fang Zheng; Yi-Ji Liao; Mu-Yan Cai; Tian-Hao Liu; Shu-Peng Chen; Pei-Hong Wu; Long Wu; Xiu-Wu Bian; Xin-Yuan Guan; Yi-Xin Zeng; Yun-Fei Yuan; Hsiang-Fu Kung; Dan Xie
• Keywords: HCCS

Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability these small RNAs modulate cellular behavior. However, efficacy miR-101 replacement hepatocellular carcinoma (HCC) remains unclear. In current study, we first observed that plasma levels were significantly lower in distant metastatic HCC patients than HCCs without metastasis, and down-regulation predicted a worse disease-free survival (DFS, P<0.05). an animal model HCC, demonstrated systemic delivery lentivirus-mediated abrogated growth liver, intrahepatic metastasis lung mediastinum, resulting dramatic suppression development mice toxicity extending life expectancy. Furthermore, enforced overexpression cells not only decreased EZH2, COX2 STMN1, but also directly down-regulated novel target ROCK2, inhibited Rho/Rac GTPase activation, blocked epithelial-mesenchymal transition (EMT) angiogenesis, inducing strong abrogation tumorigenesis aggressiveness both vitro vivo. These results provide proof-of-concept support for as powerful anti-HCC therapeutic modality by repressing multiple molecular targets.