The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation
| Autor: | Alan Mackay, Katie F. Loveson, Ilaria Alborelli, Massimiliano Manzo, Helen L. Fillmore, Rebecca L. Mather, David Roig-Carles, Ella Waters, Chris Jones, Francesco Crea, Jon P. Golding, Holly Jackson |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Biology Malignancy medicine.disease_cause Article Catalysis Histones Inorganic Chemistry lncRNA microRNA medicine Brain Stem Neoplasms Humans Epigenetics Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Cells Cultured Spectroscopy Cell Proliferation brain cancer Mutation Gene knockdown epigenetics Cell growth Organic Chemistry Glioma General Medicine medicine.disease Long non-coding RNA female genital diseases and pregnancy complications Computer Science Applications Gene Expression Regulation Neoplastic diffuse midline glioma Chemistry MicroRNAs Cell culture embryonic structures Cancer research DIPG RNA Long Noncoding paediatric glioma |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 17 International Journal of Molecular Sciences, Vol 22, Iss 9165, p 9165 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22179165 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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