C/EBPβ mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas

被引：19

作者：

Di Pascale, Federica ^{[1
,2
]}

Nama, Srikanth ^{[1
]}

Muhuri, Manish ^{[1
]}

Quah, Shan ^{[1
]}

Ismail, Hisyam M. ^{[1
]}

Chan, Xin Hui Derryn ^{[1
]}

Sundaram, Gopinath M. ^{[1
]}

Ramalingam, Rajkumar ^{[1
]}

Burke, Brian ^{[1
]}

Sampath, Prabha ^{[1
,2
,3
]}

机构：

[1] ASTAR, Inst Med Biol, Singapore 138648, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore

[3] Duke NUS Med Sch, Program Canc & Stem Cell Biol, 8 Coll Rd, Singapore 169857, Singapore

来源：

NUCLEIC ACIDS RESEARCH | 2018年 / 46卷 / 01期

关键词：

GENES; IDENTIFICATION; MICRORNAS; BINDING;

D O I：

10.1093/nar/gkx1105

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta (C/EBP beta) 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/EBP beta via an embedded 'C/EBP beta responsive element' (CRE). CRE and the Pol III B-box element overlap, suggesting that C/EBP beta 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.

引用

页码：336 / 349

页数：14

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