Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma

Fiaschetti, Giulio; Abela, Lucia; Nonoguchi, Naosuke; Dubuc, Adrian M.; Remke, Marc; Boro, Aleksandar; Grunder, E; Siler, Ulrich; Ohgaki, Hideaki; Taylor, Michael D.; Baumgärtner, Martin; Shalaby, Tarek; Grotzer, Michael A.

doi:10.1038/bjc.2013.764

Cited by 47 publications

(36 citation statements)

References 73 publications

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“…Our recent findings further demonstrated that the human R antigen post-transcriptionally regulates the expression of miR-7 (17). In addition, recent evidence indicated that histone methylation or CpG methylation may affect the expression of distinct miRNA molecules in certain types of cancers (27,28). Therefore, the predominant mechanism involved in the repressed expression of the miR-7 gene remains to be fully elucidated in future studies.…”

Section: Promoter Mutation Is Associated With Repressed Expression Ofsupporting

confidence: 52%

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Zhao

Wang

Liao

et al. 2015

Molecular and Clinical Oncology

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Abstract. The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the downregulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G→C change at the -617 site (25/39, 64.1%) and an A→G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR-7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of specific miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and therapeutic strategies against lung cancer.

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Section: Promoter Mutation Is Associated With Repressed Expression Ofsupporting

confidence: 52%

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Zhao

Wang

Liao

et al. 2015

Molecular and Clinical Oncology

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“…Both the identification and functional characterization of distinct miRNAs in human MB have been extensively reported . Likewise, the role of miRNA in CSCs has been described in several tumors .…”

Section: Discussionmentioning

confidence: 99%

miR-135a Inhibits Cancer Stem Cell-Driven Medulloblastoma Development by Directly Repressing Arhgef6 Expression

et al. 2015

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microRNAs (miRNAs) are short noncoding RNAs, which regulate gene expression post‐transcriptionally and play crucial roles in relevant biological and pathological processes. Here, we investigated the putative role of miRNAs in modulating the tumor‐initiating potential of mouse medulloblastoma (MB)‐derived cancer stem cells (CSCs). We first subjected bona fide highly tumorigenic (HT) CSCs as well as lowly tumorigenic MB CSCs and normal neural stem cells to miRNA profiling, which identified a HT CSC‐specific miRNA signature. Next, by cross‐checking CSC mRNA/miRNA profiles, we pinpointed miR‐135a as a potential tumor suppressor gene, which was strongly downregulated in HT CSCs as well as in the highly malignant experimental tumors derived from them. Remarkably, enforced expression of miR‐135a in HT CSCs strongly inhibited tumorigenesis by repressing the miR‐135a direct target gene Arhgef6. Considering the upregulation of Arhgef6 in human MBs and its involvement in mediating experimental medulloblastomagenesis, its efficient suppression by miR‐135a might make available an effective therapeutic strategy to selectively impair the tumorigenic potential of MB CSCs. Stem Cells 2015;33:1377–1389

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“…The specific miRNA expression signatures in brain tumours have received great attention in the last few years and can facilitate the diagnosis and prediction of the therapy response and prognosis [10]. It has been reported that the expression of some miRNAs is associated with survival in medulloblastoma patients [11,13,14]. …”

Section: Introductionmentioning

confidence: 99%

MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma

Yun

Zhao

Liu

et al. 2015

Cell Physiol Biochem

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Background: Alterations in the expression level of miR-495 were recently observed in various tumours. Medulloblastoma is the most common malignant brain tumour in children. However, the clinical significance of miR-495 in medulloblastomas remains unclear. Methods: The expression levels of miR-495 was examined in 62 archival formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens using TaqMan Real-time Quantitative PCR arrays. Immunohistochemistry was used to determine the expression of Gfi1 in medulloblastoma tissues, and a luciferase reporter assay was carried out to confirm whether Gfi1 is a direct target of miR-495. Results: MiR-495 expression is repressed in medulloblastoma samples compared with normal cerebellum tissues. Furthermore, patients with a low level of miR-495 showed significantly poorer survival, as determined by the log-rank test (P = 0.033). The multivariate analysis results showed that the miR-495 expression levels were an independent predictor of overall survival in medulloblastoma patients (P = 0.027; hazard ratio = 0.267). Our study provides the first demonstration that miR-495 directly interacts with the Gfi1 3'UTR to regulate Gfi1 at a post-transcriptional level and that the expression level of miR-495 is inversely correlated with the Gfi1 protein level in medulloblastoma specimens. Conclusion: Our results suggest that miR-495 may be a prognostic predictor in medulloblastoma and that Gfi1 is a potential functional target of miR-495.

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Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma

Cited by 47 publications

References 73 publications

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer

miR-135a Inhibits Cancer Stem Cell-Driven Medulloblastoma Development by Directly Repressing Arhgef6 Expression

MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma

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