MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in human glioblastoma

Wang, Xingqiang; Wang, Enqin; Cao, Jun; Xiong, Feng; Yang, Yonglin; Liu, Haitao

doi:10.18632/oncotarget.21442

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…ADAM19 encodes a metalloprotease that belongs to the ADAM family associated with cancer progression 24 . This protein has been associated with EMT in a glioblastoma model where its silencing by the miR-145 inhibited EMT 25 . Interestingly, the epigenetic signature of these seven genes was identical whichever the cell model and the inducer used.…”

Section: Discussionmentioning

confidence: 99%

EMT is associated with an epigenetic signature of ECM remodeling genes

et al. 2019

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Type III epithelial–mesenchymal transition (EMT) has been previously associated with increased cell migration, invasion, metastasis, and therefore cancer aggressiveness. This reversible process is associated with an important gene expression reprogramming mainly due to epigenetic plasticity. Nevertheless, most of the studies describing the central role of epigenetic modifications during EMT were performed in a single-cell model and using only one mode of EMT induction. In our study, we studied the overall modulations of gene expression and epigenetic modifications in four different EMT-induced cell models issued from different tissues and using different inducers of EMT. Pangenomic analysis (transcriptome and ChIP–sequencing) validated our hypothesis that gene expression reprogramming during EMT is largely regulated by epigenetic modifications of a wide range of genes. Indeed, our results confirmed that each EMT model is unique and can be associated with a specific transcriptome profile and epigenetic program. However, we could select some genes or pathways that are similarly regulated in the different models and that could therefore be used as a common signature of all EMT models and become new biomarkers of the EMT phenotype. As an example, we can cite the regulation of gene-coding proteins involved in the degradation of the extracellular matrix (ECM), which are highly induced in all EMT models. Based on our investigations and results, we identified ADAM19 as a new biomarker of in vitro and in vivo EMT and we validated this biological new marker in a cohort of non-small lung carcinomas.

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Section: Discussionmentioning

confidence: 99%

EMT is associated with an epigenetic signature of ECM remodeling genes

et al. 2019

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“…MiR-145 could inhibit cell invasion and migration by targeting TWIST in Colorectal Cancer [32], TGFBR2/Smad3 axis in bladder cancer [33], phospholipase C epsilon 1 in esophageal squamous cell carcinoma [34], ADAM19 in glioblastoma [35], and TGF-β1 in breast cancer [36].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

Zhao

Zhou

et al. 2020

Bioengineered

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Neuroblastoma (NB) is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). It is well known that miR-145 functions as a tumor suppressor in several types of cancer. However, the impact of miR-145 on NB is still ambiguous. Our aim was to investigate the potential tumor suppressive role and mechanisms of miR-145 in high-risk neuroblastoma. Expression levels of miR-145 in tissues and cells were determined using RT-qPCR. The effect of miR-145 on cell viability was evaluated using MTT assays, apoptosis levels were determined using TUNEL staining, and the MTDH protein expression was determined using western blot and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting for MTDH. The results showed that miR-145 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and low miR-145 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-145 reduced cell viability and increased apoptosis in SH-SY-5Y cells. We identified MTDH as a direct target for miR-145 in SH-SY-5Y cells. Targeting MTDH has the similar results as miR-145 overexpression. Our findings suggest that low miR-145 expression was associated with poor prognosis in patients with NB, and the overexpression of miR-145 inhibited NB cells growth by down-regulating MTDH, thus providing a potential target for the development of microRNA-based approach for NB therapy.

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“…Some miRNAs modulate the expression of genes, such as E-CADHERIN, MMP9, MMP14, SLUG, MMP2, and SNAIL, that are associated with GBM invasion and PMT 118 . In contrast, miRNAs can inhibit MT by directly targeting and inhibiting the expression of factors such as the FZD6 and FZD7 receptors 119,120 ; the transcription inhibitors ZEB1 and ZEB2 121,122 ; proteins such as Smad2, LHFPL3, and ADAM19 [123][124][125] ; and factors associated with TGF-β 126,127 and NF-κB 128,129 pathways. Furthermore, some miRNAs are involved in cell-to-cell communication and intercellular interactions mediating MT in GBM 130 .…”

Section: Micrornas (Mirnas)mentioning

confidence: 99%

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

Xu,

Hou,

et al. 2024

Cancer Biol Med

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Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.

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MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in human glioblastoma

Cited by 12 publications

References 22 publications

EMT is associated with an epigenetic signature of ECM remodeling genes

EMT is associated with an epigenetic signature of ECM remodeling genes

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

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