Linked Life Data

18384814

Source:http://linkedlifedata.com/resource/pubmed/id/18384814

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-4-28
pubmed:abstractText
miR-21 has been reported to be highly expressed in various cancers and to be inducible in a human promyelocytic cell line, HL-60, after phorbol 12-myristate 13-acetate (PMA) treatment. To examine molecular mechanisms involved in miR-21 expression, we analyzed the structure of the miR-21 gene by determining its promoter and primary transcripts. We show that activation protein 1 (AP-1) activates the miR-21 transcription in conjugation with the SWI/SNF complex, after PMA stimulation, through the conserved AP-1 and PU.1 binding sites in the promoter identified here. The previous findings of enhanced miR-21 expression in several cancers may therefore reflect the elevated AP-1 activity in these carcinomas. A single precursor RNA containing miR-21 was transcribed just downstream from the TATA box in this promoter, which is located in an intron of a coding gene, TMEM49. More important, expression of this overlapping gene is completely PMA-independent and all its transcripts are polyadenylated before reaching the miR-21 hairpin embedding region, indicating that miRNAs could have their own promoter even if overlapped with other genes. By available algorithms that predict miRNA target using a conservation of sequence complementary to the miRNA seed sequence, we next predicted and confirmed that the NFIB mRNA is a target of miR-21. NFIB protein usually binds the miR-21 promoter in HL-60 cells as a negative regulator and is swept off from the miR-21 promoter during PMA-induced macrophage differentiation of HL-60. The translational repression of NFIB mRNA by miR-21 accelerates clearance of NFIB in parallel with the simultaneous miR-21-independent transcriptional repression of NFIB after PMA stimulation. Since exogenous miR-21 expression moderately induced endogenous miR-21, an evolutionarily conserved double-negative feedback regulation would be operating as a mechanism to sustain miR-21 expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
378
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
492-504
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism.
pubmed:affiliation
Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't