The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation.
Date
2021-08-25Author
Roig-Carles, D
Jackson, H
Loveson, KF
Mackay, A
Mather, RL
Waters, E
Manzo, M
Alborelli, I
Golding, J
Jones, C
Fillmore, HL
Crea, F
Type
Journal Article
Metadata
Show full item recordAbstract
Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.
Collections
Subject
DIPG
brain cancer
diffuse midline glioma
epigenetics
lncRNA
paediatric glioma
Brain Stem Neoplasms
Cell Proliferation
Cells, Cultured
Gene Expression Regulation, Neoplastic
Glioma
Histones
Humans
MicroRNAs
Mutation
RNA, Long Noncoding
Research team
Glioma Team
Language
eng
Date accepted
2021-08-19
License start date
2021-08-25
Citation
International Journal of Molecular Sciences, 2021, 22 (17), pp. 9165 -
Publisher
MDPI