MiR-215, an activator of the CTNNBIP1/β-catenin pathway, is a marker of poor prognosis in human glioma

Tong, Yong; Liu, Bei; Hong, Zheng; Gu, Jian; Liu, Huan; Feng, Li; Tan, Bi Hua; Hartman, Melanie; Song, Chunhua; Li, Yan

doi:10.18632/oncotarget.4622

Cited by 31 publications

(24 citation statements)

References 33 publications

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“…Two recent studies reveal that miR-215-5p up-regulation in gliomas is associated with poor prognosis [31, 32]. Consistently, we also find that miR-215-5p is up-regulated in gliomas and miR-215-5p level is higher in high-grade gliomas.…”

Section: Discussionsupporting

confidence: 90%

Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas

Wang

Chen

et al. 2016

Oncotarget

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The clinical prognosis of malignant gliomas is poor and PCDH9 down-regulation is strongly associated with its poor prognosis. But the mechanism of PCDH9 down-regulation is unknown. Abnormal miRNAs profiles regulate tumor phenotypes through inhibiting their target genes and miRNAs could inhibit target genes more efficiently by binding to both the promoter and 3′UTR of target genes. In this study, to search the dual inhibitory miRNAs which suppress PCDH9 expression in gliomas, we performed an integrative analysis of databases including miRDB, TargetScan, microPIR and miRCancer. We identified three candidate miRNAs which were predicted to bind both the promoter and 3′UTR of PCDH9 and up-regulated in gliomas. Then, we validated miR-215-5p up-regulation and PCDH9 down-regulation in glioma samples and demonstrated that miR-215-5p could inhibit the mRNA and protein levels of PCDH9 in glioma cell lines by targeting its promoter and 3′ UTR at the same time. Moreover, miR-215-5p could increase glioma cell proliferation, clone formation, in-vitro migration and reduce apoptosis via inhibiting PCDH9 expression. Our study provides evidence for a novel dual inhibition of PCDH9 by miR-215-5p in gliomas and suggests that miR-215-5p might be a therapeutic target for the treatment of gliomas.

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Section: Discussionsupporting

confidence: 90%

Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas

Wang

Chen

et al. 2016

Oncotarget

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“…Importantly, we conducted in situ hybridization (ISH) analyses to examine levels of miR-215 on GBM tissue microarrays and found that higher level of miR-215 expression was correlated with poor survival (Figure 1D). The clinical importance of miR-215 in gliomagenesis is also supported by a recent report that miR-215 expression is positively correlated with poor prognosis in glioma patients (Tong et al, 2015). In sum, these data strongly indicate that miR-215 is a hypoxia-induced miRNA in GICs, and it acts to promote GBM progression probably by mediating the hypoxic responses of GICs.…”

Section: Resultsmentioning

confidence: 66%

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

et al. 2016

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SUMMARY The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.

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“…Therefore, we searched miR-215 target genes by miRTarBase or those that may be linked to immunological surveillance or residual CML stem cells; miR-215 has previously been demonstrated to be dysregulated in several human malignancies and to be correlated with tumor progression [ 19 , 21 , 26 , 27 ]. Meta-analyses have revealed that elevated miR-215 expression is correlated with poor prognosis in renal cell carcinomas [ 28 ], glioma [ 29 ] and pancreatic cancer [ 30 ]. In contrast, decreased expression was associated with advanced disease stage in colorectal cancer [ 31 ], and miR-192-5p/215 is a putative tumor suppressor in non-small cell lung cancer [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib

Ohyashiki

Umezu

Katagiri

et al. 2016

IJMS

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Approximately 40% of chronic myeloid leukemia (CML) patients who discontinue imatinib (IM) therapy maintain undetectable minimal residual disease (UMRD) for more than one year (stopping IM (STOP-IM)). To determine a possible biomarker for STOP-IM CML, we examined plasma miRNA expression in CML patients who were able to discontinue IM. We first screened candidate miRNAs in unselected STOP-IM patients, who had sustained UMRD after discontinuing IM for more than six months, in comparison with healthy volunteers, by using a TaqMan low-density array for plasma or exosomes. Exosomal miR-215 and plasma miR-215 were downregulated in the STOP-IM group compared to the control, indicating that the biological relevance of the plasma miR-215 level is equivalent to that of the exosomal level. Next, we performed real-time quantitative RT-PCR in 20 STOP-IM patients, 32 patients with UMRD on continued IM therapy (IM group) and 28 healthy volunteers. The plasma miRNA-215 level was significantly downregulated in the STOP-IM group (p < 0.0001); we determined the cut-off level and divided the IM group patients into two groups according to whether the plasma miR-215 was downregulated or not. The IM group patients with a low plasma miR-215 level had a significantly higher total IM intake, compared to the patients with elevated miR-215 levels (p = 0.0229). Functional annotation of miR-215 target genes estimated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatic tools involved cell cycle, mitosis, DNA repair and cell cycle checkpoint. Our study suggests a possible role of miR-215 in successful IM discontinuation.

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MiR-215, an activator of the CTNNBIP1/β-catenin pathway, is a marker of poor prognosis in human glioma

Cited by 31 publications

References 33 publications

Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas

Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib

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