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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2010-9-2
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pubmed:abstractText |
MicroRNAs (miRNAs) play critical roles in embryonic development and are frequently deregulated in human cancers. The let-7 family members are tumor-suppressing miRNAs and are frequently downregulated in cancer cells. Lin-28 and Lin-28B are RNA-binding proteins highly expressed in embryonic tissues. Lin-28 proteins block let-7 precursors from being processed to mature miRNAs by inducing terminal uridylation and degradation of let-7 precursors. Here, we report that Lin-28B, but not Lin-28, is highly expressed in hepatocellular carcinoma (HCC). Lin-28B expression was more frequently noted in high-grade HCCs with high alpha-fetoprotein levels. Knockdown of Lin-28B by RNA interference in the HCC cell line HCC36 suppressed proliferation in vitro and reduced in vivo tumor growth in NOD/SCID mice. In contrast, overexpression of Lin-28B in the HCC cell line HA22T enhanced tumorigenicity. Overexpression of Lin-28B also induced epithelial-mesenchymal transition in HA22T cells and hence, invasion capacity. Large-scale real-time PCR array analysis revealed that, among 380 miRNAs, only let-7/mir-98 family members were regulated by Lin-28B. Lin-28B overexpression enhanced the expression of the known let-7 targets c-myc and HMGA2. It was also found that Lin-28B enhanced the expression of type 1 insulin-like growth factor receptor in a let-7-dependent manner. These results indicate that Lin-28B regulates tumor formation and invasion in HCC through coordinated repression of the let-7/mir-98 family and induction of multiple oncogenic pathways.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HMGA2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/LIN-28 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lin-28 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN98 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/mirnlet7 microRNA, human
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1460-2180
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1516-22
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pubmed:meshHeading |
pubmed-meshheading:20525879-Adolescent,
pubmed-meshheading:20525879-Adult,
pubmed-meshheading:20525879-Aged,
pubmed-meshheading:20525879-Aged, 80 and over,
pubmed-meshheading:20525879-Animals,
pubmed-meshheading:20525879-Apoptosis,
pubmed-meshheading:20525879-Blotting, Western,
pubmed-meshheading:20525879-Carcinoma, Hepatocellular,
pubmed-meshheading:20525879-Cell Adhesion,
pubmed-meshheading:20525879-Cell Movement,
pubmed-meshheading:20525879-Cell Proliferation,
pubmed-meshheading:20525879-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20525879-HMGA2 Protein,
pubmed-meshheading:20525879-Humans,
pubmed-meshheading:20525879-Liver Neoplasms,
pubmed-meshheading:20525879-Male,
pubmed-meshheading:20525879-Mice,
pubmed-meshheading:20525879-Mice, Inbred NOD,
pubmed-meshheading:20525879-Mice, SCID,
pubmed-meshheading:20525879-MicroRNAs,
pubmed-meshheading:20525879-Middle Aged,
pubmed-meshheading:20525879-Neoplasm Invasiveness,
pubmed-meshheading:20525879-RNA, Messenger,
pubmed-meshheading:20525879-RNA-Binding Proteins,
pubmed-meshheading:20525879-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20525879-Xenograft Model Antitumor Assays,
pubmed-meshheading:20525879-Young Adult
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pubmed:year |
2010
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pubmed:articleTitle |
Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma.
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pubmed:affiliation |
Graduate Institute of Pathology, National Taiwan University, Taipei 100, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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