The role of Ets2 transcription factor in the induction of microRNA-155 by LPS, and its targeting by IL-10.
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Journal ArticleDate:
2014Access:
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Quinn SR, Mangan NE, Caffrey BE, Gantier MP, Williams BR, Hertzog PJ, McCoy CE, O'Neill LA., The role of Ets2 transcription factor in the induction of microRNA-155 by LPS, and its targeting by IL-10., The Journel of Biological Chemistry, 289, 9, 2014, 4316-4325Download Item:
Abstract:
MicroRNA-155 (miR-155) is highly
expressed in many cancers such as B cell
lymphomas and myeloid leukaemia, and
inflammatory disorders such as
rheumatoid arthritis, atopic dermatitis
and multiple sclerosis. The role of miR-
155 as both a promoter of inflammation
and an oncogenic agent provides a clear
need for miR-155 itself to be stringently
regulated. We therefore investigated the
transcriptional regulation of miR-155 in
response to the respective pro- and antiinflammatory
mediators LPS and IL-10.
Bioinformatic analysis revealed Ets
binding sites on the miR-155 promoter,
and we found that Ets2 is critical for miR-
155 induction by LPS. Truncation and
mutational analysis of the miR-155
promoter confirmed the role of the Ets2
binding site proximal to the transcription
start site for LPS responsiveness. We
observed increased binding of Ets2 to the
miR-155 promoter and Ets2 deficient
mice displayed decreased induction of
miR-155 in response to LPS. IL-10
inhibited the induction of Ets2 mRNA
and protein by LPS, thereby decreasing
Ets2 function on the pri-155 promoter.
We have thus identified Ets2 as a key
novel regulator in both the positive and
negative control of miR-155 in the
inflammatory response.
Sponsor
Grant Number
Australian Research Council (ARC)
Science Foundation Ireland (SFI)
European Research Council (ERC)
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/laoneillDescription:
PUBLISHEDSponsor:
Australian Research Council (ARC)Science Foundation Ireland (SFI)
European Research Council (ERC)
Health Research Board (HRB)
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Series/Report no:
The Journel of Biological Chemistry289
9
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Full text availableKeywords:
MicroRNA-155Subject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1074/jbc.M113.522730Metadata
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