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Title: | TRANSCRIPTIONAL REGULATION OF ONCOMIR-138 IN MALIGNANT GLIOMAS | Authors: | DI PASCALE FEDERICA | ORCID iD: | orcid.org/0000-0002-3253-7860 | Keywords: | malignant gliomas, miRNAs, transcriptional regulation, RNA Polymerase III, C/EBPβ, signalling pathways | Issue Date: | 18-Aug-2017 | Citation: | DI PASCALE FEDERICA (2017-08-18). TRANSCRIPTIONAL REGULATION OF ONCOMIR-138 IN MALIGNANT GLIOMAS. ScholarBank@NUS Repository. | Abstract: | There are compelling evidences suggesting that aberrant expression of miRNAs is linked to the initiation and progression of malignant gliomas. Recurrence of gliomas have been ascribed to a therapy-resistant subpopulation of glioma stem cells (GSCs). We previously identified microRNA-138 (miR-138) as a prosurvival oncomiR expressed by GSCs. Sequence-specific inhibition of miR-138 prevented tumorsphere formation in vitro and impeded tumorigenesis in vivo. However, the precise molecular mechanism regulating miR-138 transcription in glioma remains unexplored. Here we report the identification of the transcription factor C/EBPβ as a critical regulator of miR-138 expression. We define the function of a unique C/EBPβ binding site embedded in the DNA sequence encoding for miR-138 primary precursor. Knockdown of C/EBPβ prevents tumor growth in vivo by decreasing miR-138 expression. Further dissecting the molecular pathway, we finally demonstrate that C/EBPβ direct interaction with RNA Pol-III complex mediates transcription of oncomiR-138 and other small non-coding RNAs in malignant gliomas. | URI: | http://scholarbank.nus.edu.sg/handle/10635/137921 |
Appears in Collections: | Ph.D Theses (Open) |
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