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Open Access Highly Accessed Research article

Identification of an NF-κB p50/p65-responsive site in the human MIR155HG promoter

Ryan C Thompson, Iosif Vardinogiannis and Thomas D Gilmore*

Author Affiliations

Department of Biology, Boston University, Boston, MA 02215, USA

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BMC Molecular Biology 2013, 14:24  doi:10.1186/1471-2199-14-24

Published: 23 September 2013

Abstract

Background

MicroRNA-155 (miR-155) is the diced product of the MIR155HG gene. miR-155 regulates the expression of many immune-specific transcripts, is overexpressed in many human lymphomas, and has oncogenic activity in mouse transgenic models. MIR155HG has been proposed to be a target gene for transcription factor NF-κB largely due to the positive correlation between high nuclear NF-κB activity and increased miR-155 expression following treatment with NF-κB inducers or in subsets of hematopoietic cancers. Nevertheless, direct regulation of the human MIR155HG promoter by NF-κB has not been convincingly demonstrated previously.

Results

This report shows that induction of NF-κB activity rapidly leads to increased levels of both primary MIR155HG mRNA and mature miR-155 transcripts. We have mapped an NF-κB-responsive element to a position approximately 178 nt upstream of the MIR155HG transcription start site. The -178 site is specifically bound by the NF-κB p50/p65 heterodimer and is required for p65-induced reporter gene activation. Moreover, the levels of miR-155 in nine human B-lymphoma cell lines generally correlate with increased nuclear NF-κB proteins.

Conclusion

Overall, the identification of an NF-κB-responsive site in the MIR155HG proximal promoter suggests that MIR155HG is a direct NF-κB target gene in vivo. Understanding NF-κB-mediated regulation of miR-155 could lead to improved immune cell-related diagnostic tools and targeted therapies.

Keywords:
miR-155; MIR155HG; BIC; NF-kappaB; Promoter; Transcriptional activation