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MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial-mesenchymal transition in lung cancer cells.

ABSTRACT: Background:It is clearly necessary to discover prognostic biomarkers to identify stage I patients at risk of recurrence and give them timely postoperative treatment. Materials and methods:Data of stage I lung adenocarcinoma were retrieved from four gene series in Gene Expression Omnibus (GEO) database (GSE50081, GSE30219, GSE37745, and GSE13213). Partek Genomics Suite software was used to identify survival-related genes for finding candidate indicators for early-stage patients at risk of recurrence. Differential expression of MTBP (MDM2 binding protein) in early-stage lung adenocarcinoma tissues was determined by immunohistochemical staining. The effects of MTBP interference expression and overexpression on viability, migration, and invasion capacity of lung cells were evaluated using Cell Counting Kit-8, wound healing, and Transwell assays. The tumor growth and lung metastasis in vivo were observed in chick embryo chorioallantoic membrane model. Human Exon 2.0 ST Array was used to analyze downstream regulation genes of MTBP in lung cancer cells. Involvement of ZEB2 and epithelial-mesenchymal transition (EMT) markers was investigated by Western blot. Results:By mining GEO database, we identified MTBP as a poor prognostic indicator of stage I lung adenocarcinomas. In addition, increased expression of MTBP was also associated with poor survival in our early-stage lung adenocarcinoma cohort. Further experiment suggested that knockdown of MTBP suppressed the migration and invasion of A549 and H1975 cells in vitro and in vivo, whereas overexpression of MTBP in HCC827 and PC9 cells promoted the migration and invasion in vitro and in vivo. Furthermore, ZEB2 upregulation directly activated EMT to mediate the downstream effects of MTBP involved in lung cancer cells metastasis. Conclusion:MTBP is an independent indicator for poor prognosis in stage I lung adenocarcinomas and might promote the aggressive phenotype of non-small-cell lung cancer by inducing the EMT process through upregulating ZEB2 expression.

SUBMITTER: Pan B

PROVIDER: S-EPMC6188014 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial-mesenchymal transition in lung cancer cells.

Pan Bo B Han Haibo H Wu Lina L Xiong Ying Y Zhang Jianzhi J Dong Bin B Yang Yue Y Chen Jinfeng J

OncoTargets and therapy 20181010

<h4>Background</h4>It is clearly necessary to discover prognostic biomarkers to identify stage I patients at risk of recurrence and give them timely postoperative treatment.<h4>Materials and methods</h4>Data of stage I lung adenocarcinoma were retrieved from four gene series in Gene Expression Omnibus (GEO) database (GSE50081, GSE30219, GSE37745, and GSE13213). Partek Genomics Suite software was used to identify survival-related genes for finding candidate indicators for early-stage patients at ...[more]

PMID: 30349307

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Project description:Background:Our previous studies revealed that Jagged 2 (JAG2) is involved in the regulation of migration and invasion of colon cancer cells without affecting cell proliferation. This study further explored the specific mechanism by which JAG2 promotes migration and invasion of colorectal cancer cells. Methods:JAG2 mRNA expression in different clinical stages of colorectal cancer and normal intestinal tissues was detected by quantitative PCR (QPCR). QPCR and Western Blot were used to analyze the differential expression of JAG2 mRNA and protein between normal human colon tissue cells and various colorectal cancer cells. Co-expression status of JAG2 and epithelial-mesenchymal transition (EMT) markers in colon cancer tissues and cells was analyzed. The difference between TGF-?-induced EMT model and the JAG2 overexpression model were compared in promoting migration and invasion of HT29 cells. HT29 cells were treated with EMT pathway inhibitors (LY2157299 and Slug siRNA) to identify a cross-talk between the JAG2 effect and the Notch pathway. Co-expressed genes of JAG2 in colorectal cancer cells were identified using siRNA and transcriptome microarray technology. The mutual regulation of JAG2 and the co-expressed gene PRAF2 and the regulation of the paracrine effect of exosomes were analyzed. Results:JAG2 was abnormally expressed in colorectal cancer tissues and directly related to clinical stages. Similar to the findings in tissues, the expression of both JAG2 mRNA and protein was significantly increased in the colorectal cancer cell lines compared with that of normal colorectal cell line CCD18-Co. It was shown in our cell model that JAG2 was involved in the regulation of migration and invasion independent of the canonical Notch signaling pathway. More interestingly, JAG2 also promoted the migration and invasion of colon cancer cells in a non-EMT pathway. Further analysis revealed the co-expression of JAG2 with PRAF2 in colorectal cancer cells. JAG2-rich exosomes were released from colorectal cancer cells in a PRAF2-dependent way, while these exosomes regulated the metastasis of colorectal cancer cells in a paracrine manner. Conclusions:This is the evidence supporting the biological function of JAG2 through non-canonical Notch and non-EMT-dependent pathways and also the first demonstration of the functions of PRAF2 in colorectal cancer cells. These findings also provide theoretical basis for the development of small molecules or biological agents for therapeutic intervention targeting JAG2/PRAF2.

Project description:PurposeThe aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression.MethodsThe expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells.ResultsThe expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1.ConclusionFGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients.

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MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial-mesenchymal transition in lung cancer cells.

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MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial-mesenchymal transition in lung cancer cells.

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