C/EBPβ mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas. Issue 1 (10th November 2017)

• Record Type: Journal Article
• Authors: Di Pascale, Federica; Nama, Srikanth; Muhuri, Manish; Quah, Shan; Ismail, Hisyam M; Chan, Xin Hui Derryn; Sundaram, Gopinath M; Ramalingam, Rajkumar; Burke, Brian; Sampath, Prabha
• Is Part Of: Nucleic acids research. Volume 46:Issue 1(2018)
• Page Start: 336
• Page End: 349
• Publication Date: 2017-11-10
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx1105
• Languages: English
• ISSNs: 0305-1048

Abstract

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.