Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling

Han, Mingzhi; Wang, Shuai; Fritah, Sabrina; Wang, Xu; Zhou, Wenjing; Yang, Ning; Ni, Shilei; Huang, Bin; Chen, Anjing; Li, Gang; Miletić, Hrvoje; Thorsen, Frits; Bjerkvig, Rolf; Li, Xingang; Wang, Jian

doi:10.1093/brain/awz406

Cited by 112 publications

(97 citation statements)

References 57 publications

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“…H19 induced endothelial cell proliferation, migration, and tube formation in vitro, which were proved to exert an H19mir-29a-VASH2 axis to regulate the tumorigenesis [19]. In glioma, a number of lncRNAs have been found to be significantly dysregulated, such as HOTAIR, TUG1, and ECONEXIN [20][21][22][23][24]. Nevertheless, the various functions and multiple mechanisms of lncRNAs in glioma have not been explored comprehensively.…”

Section: Introductionmentioning

confidence: 99%

LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

Niu

Zhang

et al. 2020

Oncogene

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Glioma is the most common malignant tumor in the central nervous system. Altered long noncoding RNAs (lncRNAs) are playing regulatory roles in physiological and pathogenic processes in cancer. Here, we uncovered a differentially expressed lncRNA called brain cytoplasmic RNA 1 (BCYRN1), and elucidated its function and molecular mechanism in the progression and development of glioma. Three fresh tumor tissues from glioma patients and three normal brain tissues from craniocerebral trauma patients were prepared for high-throughput RNA sequencing. Differential RNA transcripts and BCYRN1 were identified by RT-qPCR in glioma samples and controls. CCK-8, colony formation assays, flow cytometry, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological function of BCYRN1 both in vitro and in vivo. Various bioinformatics analysis, dual-luciferase reporter assays, biotinylated RNA pulldown assays, and rescue experiments were conducted to reveal the underlying mechanisms of competitive endogenous RNAs (ceRNAs). 183 lncRNAs were identified with significant dysregulation in glioma and randomly selected differential RNAs were further confirmed by RT-qPCR. Among them, BCYRN1 was the most downregulated lncRNA, and its low expression positively correlated with glioma progression. Functionally, BCYRN1 overexpression inhibited cell proliferation, migration in glioma cell lines, whereas BCYRN1 depletion resulted in the opposite way. MiR-619-5p was further confirmed as the direct target of BCYRN1. Mechanistically, miR-619-5p specifically targeted the CUE domain containing protein 2 (CUEDC2), and BCYRN1/miR-619-5p suppressed glioma tumorigenesis by inactivating PTEN/AKT/p21 pathway in a CUEDC2-dependent manner. Overall, our data presented that the reduced expression of BCYRN1 was associated with poor patient outcome in glioma. BCYRN1 functioned as a ceRNA to inhibit glioma progression by sponging miR-619-5p to regulate CUEDC2 expression and PTEN/AKT/p21 pathway. Our results indicated that BCYRN1 exerted tumor suppressor potential and might be a candidate in the diagnosis and treatment of glioma.

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Section: Introductionmentioning

confidence: 99%

LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

Niu

Zhang

et al. 2020

Oncogene

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“…For example, a great deal of studies have shown that Wnt signaling pathway is abnormally activated in GBM, promoting the proliferation and invasion of GBM, and inducing resistance to temozolomide in GBM [21,22].…”

Section: Discussionmentioning

confidence: 99%

A long non-coding RNA signature predicts survival for glioblastoma as prognostic biomarkers

Z¹,

Z²,

Lu³

et al. 2020

Preprint

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Background: Glioblastoma (GBM) is one of the most fatal tumors in the central nervous system. Its prognosis is very poor. There is increasing evidence that long noncoding RNA (lncRNA) participates in the biological process of glioblastoma. Nevertheless, the role of lncRNA in predicting the prognosis of GBM is still uncertain. Methods: In this study, using RNA-Seq and clinical follow-up data of GBM patients from The Cancer Genome Atlas (TCGA), we performed differential analysis of lncRNA, univariable and multivariable Cox regression analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Ontology (GO) analysis.Results: We identified four lncRNAs closely interrelated with survival and prognosis of GBM patients. This lncRNA signature was effective in both the training set and the testing set, and it was independent to clinical factors.Conclusions: Our data suggested that the four lncRNAs could be used as promising biomarkers for predicting prognosis in GBM patients.

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“…Functional analysis revealed that silencing MIR22HG lead to inhibition of the Wnt/β-catenin signaling pathway due to the loss of miR-22-3p and miR-22-5p. Additionally, chromatin immunoprecipitation with parallel DNA sequencing analysis for MIR22HG showed enrichment of acetylation of lysine 27 on histone 3 (H3K27ac), which is a mark of transcriptionally active chromatin and was elevated in glioblastoma tissue, compared to normal brain tissue [143].…”

Section: Glioma Progressionmentioning

confidence: 99%

Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs

Zottel

Šamec

Paska

et al. 2020

Cancers

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Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of glioblastoma was achieved with large-scale expression analysis. However, due to genomic complexity and heterogeneity, transcriptomics alone is not enough to define the glioblastoma “fingerprint”, so epigenetic mechanisms are being examined, including the noncoding genome. On the basis of their tissue specificity, long noncoding RNAs (lncRNAs) are being explored as new diagnostic and therapeutic targets. In addition, growing evidence indicates that lncRNAs have various roles in resistance to glioblastoma therapies (e.g., MALAT1, H19) and in glioblastoma progression (e.g., CRNDE, HOTAIRM1, ASLNC22381, ASLNC20819). Investigations have also focused on the prognostic value of lncRNAs, as well as the definition of the molecular signatures of glioma, to provide more precise tumor classification. This review discusses the potential that lncRNAs hold for the development of novel diagnostic and, hopefully, therapeutic targets that can contribute to prolonged survival and improved quality of life for patients with glioblastoma.

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Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling

Cited by 112 publications

References 57 publications

LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

A long non-coding RNA signature predicts survival for glioblastoma as prognostic biomarkers

Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs

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