C/EBPβ Mediates RNA Polymerase III-driven Transcription of oncomiR-138 in Malignant Gliomas

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C/EBPβ Mediates RNA Polymerase III-driven Transcription of oncomiR-138 in Malignant Gliomas
Title:
C/EBPβ Mediates RNA Polymerase III-driven Transcription of oncomiR-138 in Malignant Gliomas
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Publication Date:
09 January 2018
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Abstract:
MicroRNA-138 (miR-138) is a pro-survival oncomiR for glioma stem cells. In malignant gliomas, dysregulated expression of microRNAs, such as miR-138, promotes Tumour initiation and progression. Here, we identify the ancillary role of the CCAAT/enhancer binding protein β (C/EBPβ) as a transcriptional activator of miR-138. We demonstrate that a short 158 bp DNA sequence encoding the precursor of miR-138-2 is essential and sufficient for transcription of miR-138. This short sequence includes the A-box and B-box elements characteristic of RNA Polymerase III (Pol III) promoters, and is also directly bound by C/EBPβ via an embedded ‘C/EBPβ responsive element’ (CRE). CRE and the Pol III B-box element overlap, suggesting that C/EBPβ and transcription factor 3C (TFIIIC) interact at the miR-138-2 locus. We propose that this interaction is essential for the recruitment of the RNA Pol III initiation complex and associated transcription of the oncomiR, miR-138 in malignant gliomas.
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http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research is Supported by Institute of Medical Biology (IMB), A*star. Grant number is not applicable
Description:
This article is available online: https://doi.org/10.1093/nar/gkx1105
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