FOXD3 is a novel tumor suppressor that affects growth, invasion, metastasis and angiogenesis of neuroblastoma

Li, Dan; Hong, Mei; Qi, Meng; Yang, Dehua; Zhao, Xiang; Xuan, Xuenan; Pu, Jiarui; Huang, Kai; Zheng, Liduan; Tong, Qiangsong

doi:10.18632/oncotarget.1579

Cited by 64 publications

(101 citation statements)

References 47 publications

(71 reference statements)

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“…Mutation of miR-584-5p binding site was established with GeneTailor™ Site-Directed Mutagenesis System (Invitrogen) and PCR primers (Supplementary Table S2). Dual-luciferase assay was performed as previously described [11,21,[27][28][29][30]. For promoter and 3′-UTR activity, the luciferase signal was normalized by firefly/Renilla and Renilla/firefly ratio, respectively.…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) assay was performed according to the instructions of EZ-ChIP kit (Upstate Biotechnology, Temecula, CA) [27][28][29][30][31] with antibodies for AGO1, AGO2, zeste homolog 2 (EZH2), histone H3 lysine 27 trimethylation (H3K27me3), and histone H3 lysine 9 dimethylation (H3K9me2; Upstate Biotechnology). Lysates were treated with either RNase H (10 U) or RNase A (20 μg) prior to immunoprecipitation.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

“…Cell migration was photographed using 10 high-power fields, at 0, 24 h post-induction of injury. Remodeling was determined as previously described [11,21,28,31].…”

Section: Scratch Migration Assaymentioning

confidence: 99%

“…HUVECs were serum starved in RPMI1640 medium for 24 h, suspended in RPMI1640 medium preconditioned with tumor cells, added to matrigel-coated wells at the density of 5 × 10 4 cells/well, and incubated at 37°C for 18 h. Quantification of antiangiogenic activity was calculated as previously described [21,22,28].…”

Section: Tube Formation Assaymentioning

confidence: 99%

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miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14

Xuan

Hong

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Matrix metalloproteinase 14 (MMP-14) is a membrane-anchored MMP crucial for tumorigenesis and aggressiveness, and is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. Recent evidence shows the emerging roles of endogenous promoter-targeting microRNAs (miRNAs) in regulating gene transcription. However, the roles of miRNAs in the transcription of MMP-14 still remain largely unknown. In this study, through mining computational algorithm program and Argonaute-chromosome interaction dataset, we identified one binding site of miRNA-584-5p (miR-584-5p) within the MMP-14 promoter. In NB tissues, miR-584-5p was under-expressed and inversely correlated with MMP-14 expression, and was an independent prognostic factor for favorable outcome of patients. miR-584-5p precursor attenuated the expression of MMP-14 in a Dicer-dependent manner, resulting in decreased levels of vascular endothelial growth factor, in cultured NB cell lines. In addition, miR-584-5p suppressed the promoter activity of MMP-14, and mutation of miR-584-5p binding site abolished these effects. Mechanistically, miR-584-5p recruited Argonaute 2 to facilitate the enrichment of enhancer of zeste homolog 2, histone H3 lysine 27 trimethylation, and histone H3 lysine 9 dimethylation on MMP-14 promoter in NB cells, which was abolished by repressing the miR-584-5p-promoter interaction. Gain- and loss-of-function studies demonstrated that miR-584-5p suppressed the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Moreover, restoration of MMP-14 expression rescued the NB cells from changes in these biological features. Taken together, these results indicate that promoter-targeting miR-584-5p exerts tumor suppressive functions in NB through repressing the transcription of MMP-14.

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Section: Luciferase Reporter Assaymentioning

confidence: 99%

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

“…Cell migration was photographed using 10 high-power fields, at 0, 24 h post-induction of injury. Remodeling was determined as previously described [11,21,28,31].…”

Section: Scratch Migration Assaymentioning

confidence: 99%

Section: Tube Formation Assaymentioning

confidence: 99%

See 2 more Smart Citations

miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14

Xuan

Hong

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…One study demonstrated that FOXD3 regulated RND3 expression and migration properties in melanoma cells (11). Another reported that FOXD3 exhibited tumor suppressive activity that affected the growth, aggressiveness and angiogenesis of neuroblastoma through the transcriptional regulation of NDRG1 (12). However, the role of FOXD3 in lung cancer remains uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Screening of FOXD3 targets in lung cancer via bioinformatics analysis

Jiang

Liu

2017

Oncol Lett

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Abstract. The purpose of the present study was to explore the targets of forkhead box D3 (FOXD3) in lung cancer, and thus contribute to the diagnosis and therapy of the disease. The gene expression profile of GSE64513 was downloaded from the Gene Expression Omnibus database. The dataset contained 3 FOXD3 knockout A549 lung cancer cell samples and 3 normal A549 cell samples. The differentially expressed genes (DEGs) between the FOXD3-knockout and normal A549 cells were identified using the limma package in R. The alternative splicing genes (ASGs) in FOXD3-knockout samples were identified by Replicate Multivariate Analysis of Transcript Splicing software. The Database for Annotation, Visualization and Integrated Discovery was used to identify the enriched functions and pathways of DEGs and ASGs. A protein-protein interaction (PPI) network was constructed based on results from the Search Tool for the Retrieval of Interacting Genes database and visualized using Cytoscape software. A total of 1,853 DEGs and 2,249 ASGs were identified in FOXD3-knockout A549 cells compared with normal A549 cells. The DEGs were enriched in 338 Gene Ontology (GO) terms and 21 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the ASGs were enriched in 470 GO terms and 22 KEGG pathways. A total of 199 overlaps between the DEGs and the ASGs were identified; a PPI network constructed based on the overlapping genes contained 97 nodes and 115 pairs. FOXD3 may serve an important role in regulating the growth, migration and proliferation of tumor cells in lung cancer. The present study indicates that a number of genes, including AURKA and NOS3, may be targets of FOXD3, mediating its effect in lung cancer.

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Down‐regulation of miR‐26b induces cisplatin resistance in nasopharyngeal carcinoma by repressing JAG1

2016

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Therapy against nasopharyngeal carcinoma ( NPC ) is hurdled by chemoresistance. Recent studies found that micro RNA (mi RNA ) are important regulators of cancer resistance. In this study, we aimed to explore the role and mechanism of miR‐26b in regulating NPC cisplatin ( CDDP ) resistance. Real‐time PCR was used to evaluate miR‐26b levels in CDDP ‐resistant and CDDP ‐sensitive NPC cells, as well as human NPC tissues. MiR‐26b was ectopically overexpressed in CDDP ‐resistant cells, followed by monitoring changes in cell viability and apoptosis. Interaction between JAG 1 and miR‐26b was characterized by dual‐luciferase reporter assay. Furthermore, we investigated whether ectopic JAG 1 expression reversed CDDP sensitivity induced by miR‐26b overexpression. The effect of FOXD 3 down‐regulation on miR‐26b was also evaluated. Our results indicate that miR‐26b was lower in the CDDP ‐resistant NPC cells, human NPC tissue, particularly in secondary metastases. Ectopic expression of miR‐26b sensitized NPC cells to CDDP . JAG 1 is a target of miR‐26b, and its expression is inversely correlated with miR‐26b. Overexpression of JAG 1 reversed the CDDP sensitivity induced by miR‐26b overexpression. FOXD 3 expression was also down‐regulated in CDDP ‐resistant NPC . FOXD 3 promoted miR‐26b expression and down‐regulation of FOXD 3 suppressed miR‐26b expression. Down‐regulation of miR‐26b is closely correlated with the CDDP resistance in NPC .

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FOXD3 is a novel tumor suppressor that affects growth, invasion, metastasis and angiogenesis of neuroblastoma

Cited by 64 publications

References 47 publications

miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14

miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14

Screening of FOXD3 targets in lung cancer via bioinformatics analysis

Down‐regulation of miR‐26b induces cisplatin resistance in nasopharyngeal carcinoma by repressing JAG1

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