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Article: Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets

TitleSystemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets
Authors
Issue Date2015
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
PLoS Genetics, 2015, v. 11 n. 2, p. Article no. e1004873 How to Cite?
AbstractTargeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets. © 2015 Zheng et al.
Persistent Identifierhttp://hdl.handle.net/10722/210711
ISSN
2014 Impact Factor: 7.528
2015 SCImago Journal Rankings: 6.308
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, F-
dc.contributor.authorLiao, YJ-
dc.contributor.authorCai, MY-
dc.contributor.authorLiu, TH-
dc.contributor.authorChen, SP-
dc.contributor.authorWu, PH-
dc.contributor.authorWu, L-
dc.contributor.authorBian, XW-
dc.contributor.authorGuan, X-
dc.contributor.authorZeng, YX-
dc.contributor.authorYuan, YF-
dc.contributor.authorKung, HF-
dc.contributor.authorXie, D-
dc.date.accessioned2015-06-23T05:48:04Z-
dc.date.available2015-06-23T05:48:04Z-
dc.date.issued2015-
dc.identifier.citationPLoS Genetics, 2015, v. 11 n. 2, p. Article no. e1004873-
dc.identifier.issn1553-7390-
dc.identifier.urihttp://hdl.handle.net/10722/210711-
dc.description.abstractTargeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets. © 2015 Zheng et al.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/-
dc.relation.ispartofPLoS Genetics-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSystemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pgen.1004873-
dc.identifier.pmid25693145-
dc.identifier.pmcidPMC4334495-
dc.identifier.scopuseid_2-s2.0-84924354720-
dc.identifier.hkuros243535-
dc.identifier.volume11-
dc.identifier.issue2-
dc.identifier.spageArticle no. e1004873-
dc.identifier.epageArticle no. e1004873-
dc.identifier.isiWOS:000352081800004-
dc.publisher.placeUnited States-

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