Linked Life Data

21680528

Source:http://linkedlifedata.com/resource/pubmed/id/21680528

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-7-21
pubmed:abstractText
miR-155, processed from the B-cell integration cluster (BIC), is one of the few well-studied microRNAs (miRNAs) and is involved in both innate immunity and tumorigenesis. BIC/miR-155 is induced by distinct signaling pathways, but little is known about the underlying mechanisms. We have identified two conserved potential interferon (IFN) regulatory factor (IRF)-binding/interferon-stimulated response element motifs in the Bic gene promoter. Two oncogenic IRFs, IRF4 and -7, in addition to some other members of the family, bind to and significantly transactivate the Bic promoter. Correspondingly, the endogenous levels of IRF4 and -7 are correlated with that of the BIC transcript in Epstein-Barr virus (EBV)-transformed cells. However, RNA interference studies have shown that depletion of IRF4, rather than of IRF7, dramatically decreases the endogenous level of BIC by up to 70% in EBV- or human T-cell leukemia virus type 1 (HTLV1)-transformed cell lines and results in apoptosis and reduction of proliferation rates that are restored by transient expression of miR-155. Moreover, the endogenous levels of the miR-155 target, SHIP1, are consistently elevated in EBV- and HTLV1-transformed cell lines stably expressing shIRF4. In contrast, transient expression of IRF4 decreases the SHIP1 level in EBV-negative B cells. Furthermore, the level of IRF4 mRNA is significantly correlated with that of BIC in adult T-cell lymphoma/leukemia (ATLL) tumors. These results show that IRF4 plays an important role in the regulation of BIC in the context of EBV and HTLV1 infection. Our findings have identified Bic as the first miRNA-encoding gene for IRFs and provide evidence for a novel molecular mechanism underlying the IRF/BIC pathway in viral oncogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8328-37
pubmed:meshHeading
pubmed-meshheading:21680528-Adult, pubmed-meshheading:21680528-Aged, pubmed-meshheading:21680528-Apoptosis, pubmed-meshheading:21680528-B-Lymphocytes, pubmed-meshheading:21680528-Cell Line, Transformed, pubmed-meshheading:21680528-Cell Transformation, Viral, pubmed-meshheading:21680528-Female, pubmed-meshheading:21680528-HEK293 Cells, pubmed-meshheading:21680528-HeLa Cells, pubmed-meshheading:21680528-Herpesvirus 4, Human, pubmed-meshheading:21680528-Human T-lymphotropic virus 1, pubmed-meshheading:21680528-Humans, pubmed-meshheading:21680528-Interferon Regulatory Factor-7, pubmed-meshheading:21680528-Interferon Regulatory Factors, pubmed-meshheading:21680528-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:21680528-Male, pubmed-meshheading:21680528-MicroRNAs, pubmed-meshheading:21680528-Middle Aged, pubmed-meshheading:21680528-Phosphoric Monoester Hydrolases, pubmed-meshheading:21680528-Promoter Regions, Genetic, pubmed-meshheading:21680528-RNA, Messenger, pubmed-meshheading:21680528-RNA, Small Interfering, pubmed-meshheading:21680528-RNA Interference, pubmed-meshheading:21680528-Response Elements, pubmed-meshheading:21680528-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21680528-Signal Transduction
pubmed:year
2011
pubmed:articleTitle
Oncogenic IRFs provide a survival advantage for Epstein-Barr virus- or human T-cell leukemia virus type 1-transformed cells through induction of BIC expression.
pubmed:affiliation
Division of Hematology/Oncology, Viral Oncology Program, Sylvester Comprehensive Cancer Center, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. sning@med.miami.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural