Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling
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Le résumé fourni par la source
Long non-coding RNAs play critical roles in tumour progression. Through analysis of publicly available genomic datasets, we found that MIR22HG, the host gene of microRNAs miR-22-3p and miR-22-5p, is ranked among the most dysregulated long non-coding RNAs in glioblastoma. The main purpose of this work was to determine the impact of MIR22HG on glioblastoma growth and invasion and to elucidate its mechanistic function. The MIR22HG/miR-22 axis was highly expressed in glioblastoma as well as in glioma stem-like cells compared to normal neural stem cells. In glioblastoma, increased expression of MIR22HG is associated with poor prognosis. Through a number of functional studies, we show that MIR22HG silencing inhibits the Wnt/β-catenin signalling pathway through loss of miR-22-3p and -5p. This leads to attenuated cell proliferation, invasion and in vivo tumour growth. We further show that two genes, SFRP2 and PCDH15, are direct targets of miR-22-3p and -5p and inhibit Wnt signalling in glioblastoma. Finally, based on the 3D structure of the pre-miR-22, we identified a specific small-molecule inhibitor, AC1L6JTK, that inhibits the enzyme Dicer to block processing of pre-miR-22 into mature miR-22. AC1L6JTK treatment caused an inhibition of tumour growth in vivo. Our findings show that MIR22HG is a critical inducer of the Wnt/β-catenin signalling pathway, and that its targeting may represent a novel therapeutic strategy in glioblastoma patients.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling
- Date Crossref
- 31/12/2019
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Qilu Hospital of Shandong University Department of Neurosurgery pays non établi dans la noticeÉtablissement de santé
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University of Bergen Department of Biomedicine pays non établi dans la noticeUniversité ou école supérieure
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Luxembourg Institute of Health pays non établi dans la noticeOrganisation à but non lucratif
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Haukeland University Hospital Department of Pathology pays non établi dans la noticeÉtablissement de santé
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NorLux Neuro-Oncology Laboratory pays non établi dans la noticeStructure de recherche
Department of Neurosurgery — Qilu Hospital of Shandong University, Department of Biomedicine — University of Bergen et Luxembourg Institute of Health, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.