{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:13:38Z","timestamp":1788066818757,"version":"build-2784847793"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Abbie's Army","award":["Development of H19-targeting antisense oligonucleotides for DIPG therapy"],"award-info":[{"award-number":["Development of H19-targeting antisense oligonucleotides for DIPG therapy"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22179165","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:19:26Z","timestamp":1629937166000},"page":"9165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation"],"prefix":"10.3390","volume":"22","author":[{"given":"David","family":"Roig-Carles","sequence":"first","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Jackson","sequence":"additional","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-4327","authenticated-orcid":false,"given":"Katie F.","family":"Loveson","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Mackay","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Mather","sequence":"additional","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Waters","sequence":"additional","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Manzo","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7849-3958","authenticated-orcid":false,"given":"Ilaria","family":"Alborelli","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7910-7382","authenticated-orcid":false,"given":"Jon","family":"Golding","sequence":"additional","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-579X","authenticated-orcid":false,"given":"Helen L.","family":"Fillmore","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Crea","sequence":"additional","affiliation":[{"name":"Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s10555-019-09824-2","article-title":"Pediatric diffuse intrinsic pontine glioma: Where do we stand?","volume":"38","author":"Rashed","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11940-019-0577-y","article-title":"Diffuse Intrinsic Pontine Glioma: From Diagnosis to Next-Generation Clinical Trials","volume":"21","author":"Vitanza","year":"2019","journal-title":"Curr. 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