Transcription factor glioma-associated oncogene homolog 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition of non-small cell lung cancer cells

Li, Hua; Da, Lijun; Fan, Weidong; Long, Xiaohong; Zhang, Xian‐Quan

doi:10.3892/mmr.2015.3150

Cited by 9 publications

(10 citation statements)

References 43 publications

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“…EMT is the process by which epithelial cells depolarize and acquire a mesenchymal phenotype, and is a common early step in the process of metastasis [64]. EMT induction is accompanied by the up-regulation of human glioma-associated oncogene homolog 1 mRNA and protein levels [65]. The extracellular signal-regulated kinase pathway can mediate TGFβ1-induced EMT in NSCLC and may be a potential target for the treatment of NSCLC [66].…”

Section: Chromosome 19-related Protein Variation Validationmentioning

confidence: 99%

Association of chromosome 19 to lung cancer genotypes and phenotypes

Wang

Zhang

Nilsson

et al. 2015

Cancer Metastasis Rev

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The Chromosome 19 Consortium, a part of the Chromosome-Centric Human Proteome Project (C-HPP, http://www.C-HPP.org ), is tasked with the understanding chromosome 19 functions at the gene and protein levels, as well as their roles in lung oncogenesis. Comparative genomic hybridization (CGH) studies revealed chromosome aberration in lung cancer subtypes, including ADC, SCC, LCC, and SCLC. The most common abnormality is 19p loss and 19q gain. Sixty-four aberrant genes identified in previous genomic studies and their encoded protein functions were further validated in the neXtProt database ( http://www.nextprot.org/ ). Among those, the loss of tumor suppressor genes STK11, MUM1, KISS1R (19p13.3), and BRG1 (19p13.13) is associated with lung oncogenesis or remote metastasis. Gene aberrations include translocation t(15, 19) (q13, p13.1) fusion oncogene BRD4-NUT, DNA repair genes (ERCC1, ERCC2, XRCC1), TGFβ1 pathway activation genes (TGFB1, LTBP4), Dyrk1B, and potential oncogenesis protector genes such as NFkB pathway inhibition genes (NFKBIB, PPP1R13L) and EGLN2. In conclusion, neXtProt is an effective resource for the validation of gene aberrations identified in genomic studies. It promises to enhance our understanding of lung cancer oncogenesis.

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Section: Chromosome 19-related Protein Variation Validationmentioning

confidence: 99%

Association of chromosome 19 to lung cancer genotypes and phenotypes

Wang

Zhang

Nilsson

et al. 2015

Cancer Metastasis Rev

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“…Chromosome 1 is gene-dense, and it contains 3,141 genes and 991 pseudogenes, and many overlapping coding sequences. Chromosomal 1p contains genes associated with DNA damage repairing, spindle checkpoint function, apoptosis, Wnt signaling pathways, and tumor suppression5 Chromosome 19 has approximately 64 million base pairs, accounting for more than 2% of the human genome26 Chromosome 1p deletion is generally associated with the initiation of carcinogenesis7 Abnormal chromosome 19 may cause tumorigenesis through tumor suppressor gene deletion,27 DNA repair dysfunction,28 abnormal regulation of TGF-β pathway6 and NF-κB pathway29 However, in lower grade glioma, chr1p/19q co-deletion is a beneficial prognosis marker, which is not consistent with existing research. We hypothesized that during the tumorigenesis, certain “driver genes” on the chr1p/19q become activated, and their high expression leads to a worse phenotype of tumor cells, thus negatively affecting the patient’s prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…It is welll known that chr1p and chr19q contain genes associated with DNA damage repairing, spindle checkpoint function, apoptosis, WNT signaling pathways, TGF-βsignaling pathways and tumor suppression 5,6. Chromosome 1p deletion is generally associated with the initiation of carcinogenesis7 However, in lower grade glioma, chr1p/19q co-deletion is a beneficial marker to the prognosis, which is contrary to previous knowledge8 We hypothesize that the co-deletion of chr1p/19q leads to the loss of important genes during tumor development.…”

Section: Introductionmentioning

confidence: 99%

<p>Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma</p>

Zhang

et al. 2019

CMAR

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Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q. Materials and methods: The data was downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between lower grade glioma tissue and normal brain were identified. The univariate COX regression, robust likelihood-base survival analysis (rbsurv) and multivariate COX regression analysis were used to establish the 4-gene-signature based on the DEGs. The receiver operating characteristic (ROC) curve and the Kaplan-Mere curve were used to verify the prediction accuracy of the signature. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to explore the reasons for good prognosis in patients with chr1p/19q deletion. Results: A total of 1346 DEGs were identified between lower grade glioma samples and normal brain samples in GSE16011, including 56 up-regulated mRNAs located on chr1p and 20 up-regulated mRNAs located on chr19q. We established a 4-gene-signature that was significantly associated with survival based on the 76 gene. The AUC of the 4-gene-signature for 5-year OS in TCGA and CGGA was 0.837 and 0.876, respectively, which was superior compared to other parameters such as chr1p/19q co-deletion, IDH mutant, WHO grade and histology type, especially in chr1p/19q non-co-deletion patients. GSEA and KEGG analysis suggested that the prolongation of chr1p/19q in patients could be associated with cell cycle and DNA mismatch repairing. Conclusions: We established a robust 4-gene-signature based on the chr1p/19q and we explored the potential function of these newly identified survival-associated genes by bioinformatics analysis. The 4-gene from the signature are promising molecular targets to be used in the future.

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“…Emerging evidence associates chemoresistance with the acquisition of EMT in cancer [38, 39]. The induced EMT was associated with increased cell motility, invasiveness, and clonogenicity.…”

Section: Discussionmentioning

confidence: 99%

GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment

Cai

Zhao

et al. 2016

J Exp Clin Cancer Res

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BackgroundThe aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms.MethodsThe cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell proliferative capability. Apoptotic cell number was measured by flow cytometry. The transwell assay was used to test the cell invasive capability. DNA damage effect was identified by COMET assay and γH2AX expression.ResultsProliferation of tumor cells treated with GANT61 in combination with TMZ was significantly suppressed compared with those treated with either drug used alone. The combination treatment induced a higher rate of apoptosis, DNA damage and reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT and the Notch1 pathway increased in the cells treated by TMZ treatment. However, GANT61 could abrogated the protein increasing.ConclusionsGANT61 sensitizes glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT expression and the Notch1 pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0463-3) contains supplementary material, which is available to authorized users.

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Transcription factor glioma-associated oncogene homolog 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition of non-small cell lung cancer cells

Cited by 9 publications

References 43 publications

Association of chromosome 19 to lung cancer genotypes and phenotypes

Association of chromosome 19 to lung cancer genotypes and phenotypes

<p>Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma</p>

GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment

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