Source:http://linkedlifedata.com/resource/pubmed/id/21055388
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-12-6
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pubmed:abstractText |
Previous work by us and others reported decreased expression of miR-199a-3p in hepatocellular carcinoma (HCC) tissues compared to adjacent benign tissue. We report here a significant reduction of miR-199a-3p expression in 7 HCC cell lines. To determine if miR-199a-3p has a tumor suppressive role, pre-miR-199a-3p oligonucleotides were transfected into the HCC cell lines. Pre-miR-199a-3p oligonucleotide reduced cell proliferation by approximately 60% compared to control oligonucleotide in only two cell lines (SNU449 and SNU423); the proliferation of the other 5 treated cell lines was similar to control oligonucleotide. A pre-miR-199a-3p oligonucleotide formulated with chemical modifications to enhance stability while preserving processing, reduced cell proliferation in SNU449 and SNU423 to the same extent as the commercially available pre-miR-199a-3p oligonucleotide. Furthermore, only the duplex miR-199a-3p oligonucleotide, and not the guide strand alone, was effective at reducing cell viability. Since a CD44 variant was essential for c-Met signaling [V. Orian-Rousseau, L. Chen, J.P. Sleeman, P. Herrlich, H. Ponta, CD44 is required for two consecutive steps in HGF/c-Met signaling, Genes Dev. 16 (2002) 3074-3086] and c-Met is a known miR-199a-3p target, we hypothesized that miR-199a-3p may also target CD44. Immunoblotting confirmed that only the two HCC lines that were sensitive to the effects of pre-miR-199a-3p were CD44+. Direct targeting of CD44 by miR-199a-3p was confirmed using luciferase reporter assays and immunoblotting. Transfection of miR-199a-3p into SNU449 cells reduced in vitro invasion and sensitized the cells to doxorubicin; both effects were enhanced when hyaluronic acid (HA) was added to the cell cultures. An inverse correlation between the expression of miR-199a-3p and CD44 protein was noted in primary HCC specimens. The ability of miR-199a-3p to selectively kill CD44+ HCC may be a useful targeted therapy for CD44+ HCC.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/mirn199 microRNA, human
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1090-2104
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
403
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
120-5
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pubmed:dateRevised |
2011-10-6
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pubmed:meshHeading |
pubmed-meshheading:21055388-Antibiotics, Antineoplastic,
pubmed-meshheading:21055388-Antigens, CD44,
pubmed-meshheading:21055388-Carcinoma, Hepatocellular,
pubmed-meshheading:21055388-Cell Line, Tumor,
pubmed-meshheading:21055388-Cell Proliferation,
pubmed-meshheading:21055388-Doxorubicin,
pubmed-meshheading:21055388-Drug Resistance, Neoplasm,
pubmed-meshheading:21055388-Genes, Tumor Suppressor,
pubmed-meshheading:21055388-Humans,
pubmed-meshheading:21055388-Liver Neoplasms,
pubmed-meshheading:21055388-MicroRNAs,
pubmed-meshheading:21055388-Neoplasm Invasiveness
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pubmed:year |
2010
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pubmed:articleTitle |
miR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines.
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pubmed:affiliation |
Department of Surgery, Ohio State University Medical Center, Columbus, OH, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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