PAX3 is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells

Liang, Xiaofeng; Huang, Qiyu; Nie, Dekang; Shi, Jinlong; Gong, Mingjie; Wu, Bin; Gong, Peipei; Zhao, Liling; Zuo, Houjuan; Ju, Shaoqin; Chen, Jian; Shi, Wei

doi:10.1016/j.brainres.2013.05.021

Cited by 27 publications

(35 citation statements)

References 23 publications

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“…The animal study proposal was approved by the Laboratory Animal Center of Nantong University (permit number, 20140310-009). All mouse experimental procedures were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of People's Republic of China (15). In total, 21 BALB/C nude mice (4-6 weeks old; body weight, 18±2 g) were provided by the animal experimental center at Affiliated Hospital of Nantong University (Nantong, Jiangsu, China) and kept in a specific-pathogen-free facility.…”

Section: Sample Preparation and Hematoxylin And Eosin (He) Stainingmentioning

confidence: 99%

Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells

Chen

et al. 2016

Oncology Letters

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Abstract. The present study aimed to investigate the role of pituitary tumor-transforming gene 1 (PTTG1) in the proliferation, invasion and apoptosis of human malignant glioma U251 cells. Firstly, 2 microRNAs (miRNAs) targeting PTTG1 messenger (m)RNA were ligated into a pcDNA6.2-GW/EmGFP-miR expression vector. The recombinant plasmids, miRNA-1 and miRNA-2 (miR-2), were transfected into U251 cells using the liposome method. PTTG1 mRNA and protein levels were evaluated using quantitative polymerase chain reaction and western blot analysis. The proliferation and invasion abilities of U251 cells were determined using methylthiazol tetrazolium and Matrigel assays. Flow cytometry analysis with Annexin V/propidium iodide double staining was used to determine the percentage of apoptotic cells. PTTG1 expression was effectively suppressed by miR-2. U251 cell growth was inhibited between 10.7 and 34.7% in the miR-2 group compared with the blank group. The Matrigel assay demonstrated that the percentage of infiltrating U251 cells was significantly lower in the miR-2 group (12.3±1.0%) compared to the blank group (24.7±1.4%; P<0.001) and the negative control group (24.0±2.0%; P<0.05). A higher percentage of apoptotic U251 cells were observed in the miR-2 group compared with the blank group (53.6 vs. 32.4%) using flow cytometry due to cycle arrests at the G2/M phase. The miR-2-transfected U251 cells were subcutaneously injected into nude mice, and these mice possessed a decreased tumor tissue growth rate and higher percentage of apoptotic cells compared with the blank and negative control groups. In conclusion, PTTG1 gene expression in human malignant glioma U251 cells was effectively suppressed by exogenous miR-2. The downregulation of PTTG1 induced glioma cell apoptosis and cell cycle arrest at the G2/M phase, which inhibited cell proliferation, reverse invasion and infiltration of glioma cells.

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Section: Sample Preparation and Hematoxylin And Eosin (He) Stainingmentioning

confidence: 99%

Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells

Chen

et al. 2016

Oncology Letters

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“…Inhibition of PAX3 expression in glioblastoma U-87MG cells suppressed tumorigenicity and upregulation of PAX3 expression in glioma SHG-44 cells promoted tumor formation in vivo. These results indicate that PAX3 in glioma is essential for gliomagenesis; thus, targeting PAX3 or its downstream targets may lead to novel therapies for this disease [30]; this data has been represented in Table 1. PAX3 contributes to various cell lineages during embryonic development and is also important in tumourigenesis.…”

Section: Rhabdomyosarcomamentioning

confidence: 97%

“…More recently, PAX3 was observed to be overexpressed in various types of cancer tissues and cell lines like neuroblastomas, glioblastomas, melanomas, and gastric cancers, suggesting that it may function as an oncogene in these cancers [30][31][32][33][34][35][36]. In rhabdomyosarcomas, PAX3-FOXO1 fusion increases the transcriptional activity of PAX3 by constitutive nuclear localization [37].…”

Section: Introductionmentioning

confidence: 99%

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

Arasu

Murugan

Essa

et al. 2018

BioMed Research International

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Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

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“…Given that oncogenic function of PAX3 has been previously reported in other cancers such as glioblastomas and melanomas [5, 7], we attempted to determine the role of PAX3 in glioblastoma cell line U251 and melanoma cell line A375. As shown in Supplementary Figure S8, our data showed that PAX3 re-expression increased phosphorylation of Akt and FOXO3a in U251 cells and phosphorylation of Erk in A375 cells, suggesting that PAX3 plays a tumor-promoting role in glioblastomas and melanomas probably through activating these signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

“…It is now clear that there is a potential link between aberrant expression of PAX genes in adult tissues and a wide variety of cancers by promoting or inhibiting tumorigenesis [2, 3]. As a member of PAX gene family, PAX3 has been found to be correlated with oncogenesis [4], and is upregulated and highly expressed in glioblastomas, neuroblastomas, melanomas, rhabdomyosarcomas, Ewing sarcomas and gastric cancers [5–10]. These observations suggest that PAX3 may be a potential oncogene in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

PAX3 is a novel tumor suppressor by regulating the activities of major signaling pathways and transcription factor FOXO3a in thyroid cancer

et al. 2016

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Paired box 3 (PAX3) is expressed early during embryonic development in spatially restricted domains in the nervous system and in some mesodermally-derived structure. In recent years, it is found to be overexpressed in different types of cancer tissues and cell lines including glioblastomas, neuroblastomas, melanomas, rhabdomyosarcomas, Ewing sarcomas and gastric cancers, suggesting that it may function as an oncogene in these cancers. However, its role in thyroid cancer remains totally unclear. The aim of this study was to explore the functions and related molecular mechanism of PAX3 in thyroid tumorigenesis. Using quantitative RT-PCR (qRT-PCR) and Methylation-specific PCR (MSP) assays, we demonstrated that PAX3 was frequently down-regulated by promoter methylation in both primary thyroid cancer tissues and thyroid cancer cell lines. In addition, our data showed that ectopic expression of PAX3 dramatically inhibited thyroid cancer cell proliferation, colony formation, migration and invasion, induced cell cycle arrest and apoptosis and retarded tumorigenic potential in nude mice. Mechanically, PAX3 exerted its tumor suppressor function by inhibiting the activity of major signaling pathways including the phosphatidylinositol-3-kinase (PI3K)/Akt and MAPK/Erk pathways, and enhancing expression and activity of transcription factor FOXO3a. Altogether, our findings provided insight into the role of PAX3 as a novel functional tumor suppressor in thyroid cancer through modulating the activities of PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a, and demonstrated that epigenetic alterations such as promoter methylation should be a major mechanism of PAX3 inactivation in this cancer.

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PAX3 is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells

Cited by 27 publications

References 23 publications

Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells

Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

PAX3 is a novel tumor suppressor by regulating the activities of major signaling pathways and transcription factor FOXO3a in thyroid cancer

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