Oncogene In Glioma Research Articles

Up-regulation of long non-coding RNA BLACAT1 predicts aggressive clinicopathologic characteristics and poor prognosis of glioma.

Bladder cancer-associated transcript 1 (BLACAT1) is one of the most common cancer-associated long non-coding RNAs (lncRNAs), which has been reported as a tumor promotor in several malignancies. Previously, BLACAT1 was found to be overexpressed in glioma tissues and cell lines. Functional assays determined that BLACAT1 promoted glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition, suggesting that BLACAT1 might serve as an oncogene in glioma. In the present study, we aimed to investigate its clinical significance and prognostic value in glioma patients.A total of 137 paired glioma tissue samples and adjacent normal brain tissue samples were collected from 137 glioma patients who underwent surgery from May 2014 to February 2019. The Student t test was applied to determine the statistical significance of the observed differences between 2 groups. Survival curves were constructed and differences among groups were calculated using the Kaplan–Meier method.The relative expression of BLACAT1 in glioma samples was significantly higher than that of matched normal tissues (P < .001). The expression level of tissue BLACAT1 was statistically correlated with tumor size (P = .04), Karnofsky Performance Status (KPS) (P = .006), and WHO grade (P = .017). Kaplan–Meier analysis with the log-rank test revealed that BLACAT1 up-regulation was correlated with shorter overall survival time of patients with glioma (Log Rank test, P = .012). In multivariate Cox analysis, BLACAT1 expression was found to be an independent prognostic factor for overall survival in patients with glioma (HR = 2.739; 95% CI: 1.785–8.229; P = .035). Our study demonstrates that up-regulation of BLACAT1 is able to predict aggressive clinicopathologic characteristics and poor prognosis of glioma patients. These findings may have significant implications for potential treatment options and prognosis for patients with glioma.

Retraction: TRIM22 functions as an oncogene in gliomas through regulating the Wnt/β-catenin signaling pathway.

Retraction of ‘TRIM22 functions as an oncogene in gliomas through regulating the Wnt/β-catenin signaling pathway’ by Shi-lei Tang et al., RSC Adv., 2018, 8, 30894–30901, DOI: 10.1039/C8RA05684F.

Oncogenic and Tumor-Suppressive Functions of NOTCH Signaling in Glioma.

Although the role of NOTCH signaling has been extensively studied in health and disease, many questions still remain unresolved. Being crucial for tissue homeostasis, NOTCH signaling is also implicated in multiple cancers by either promoting or suppressing tumor development. In this review we illustrate the context-dependent role of NOTCH signaling during tumorigenesis with a particular focus on gliomas, the most frequent and aggressive brain tumors in adults. For a long time, NOTCH has been considered an oncogene in glioma mainly by virtue of its neural stem cell-promoting activity. However, the recent identification of NOTCH-inactivating mutations in some glioma patients has challenged this notion, prompting a re-examination of the function of NOTCH in brain tumor subtypes. We discuss recent findings that might help to reconcile the controversial role of NOTCH signaling in this disease, and pose outstanding questions that still remain to be addressed.

Diagnostic and Prognostic Potentials of Long Noncoding RNA ELF3-AS1 in Glioma Patients.

Objective Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for glioma patients. However, the potential function of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) in tumors remained largely unclear. The aim of this study was to explore the expression of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) and evaluate its functions in glioma patients. Patients and Methods. ELF3-AS1 expressions were examined by RT-PCR in 182 pairs of glioma specimens and adjacent normal tissues. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ELF3-AS1. The chi-square tests were used to examine the associations between ELF3-AS1 expression and the clinicopathological characters. The overall survival (OS) and disease-free survival (DFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. The prognostic value of the ELF3-AS1 expression in glioma patients was further analyzed using univariate and multivariate Cox regression analyses. Loss-of-function assays were performed to determine the potential function of ELF3-AS1 on the proliferation and invasion of glioma cells. Results The ELF3-AS1 expression level was significantly higher in glioma specimens compared with adjacent nontumor specimens (p < 0.01). A high expression of ELF3-AS1 was shown to be associated with the WHO grade (p = 0.023) and KPS score (p = 0.012). ROC assays revealed that high ELF3-AS1 expression had an AUC value of 0.8073 (95% CI: 0.7610 to 0.8535) for glioma. Using the Kaplan-Meier analysis, we found that patients with a high ELF3-AS1 expression had significantly poor OS (p = 0.006) and DFS (p = 0.0002). In a multivariate Cox model, we confirmed that ELF3-AS1 expression was an independent poor prognostic factor for glioma patients. The functional assay revealed that knockdown of ELF3-AS1 suppressed the proliferation and invasion of glioma cells. Conclusions Our findings confirmed that ELF3-AS1 functions as an oncogene in glioma and indicated that ELF3-AS1 is not only an important prognostic marker but also a potential therapy target for glioma.

The long noncoding RNA FTX promotes a malignant phenotype in bone marrow mesenchymal stem cells via the miR-186/c-Met axis

Gliomas are the most common and aggressive primary tumours of the central nervous system in adults. Bone marrow-derived mesenchymal stem cells (BMSCs) are an important component of the glioma microenvironment. Our previous study indicated that BMSCs in the glioma microenvironment could be induced to malignantly transform by glioma stem cells (GSCs). The malignant transformation of BMSCs is closely related to glioma progression; however, the underlying mechanism of this transformation has not been fully clarified. In this study, we found that compared with the levels in normal BMSCs, the levels of the long noncoding RNA FTX transcript XIST regulator (lncRNA-FTX) were increased in malignantly transformed BMSCs (tBMSCs), which was associated with the proliferation, migration and invasion of tBMSCs. Next, by using a luciferase reporter assay and an RNA pull-down assay, we found that lncRNA-FTX acted as a sponge for miR-186 in tBMSCs. Further research revealed that miR-186 could bind to the 3ʹ-UTR (untranslated region) of c-Met, which acts as an oncogene in gliomas. Through functional assays, we showed that lncRNA-FTX could regulate c-Met expression in tBMSCs in a miR-186-dependent manner. Based on these data, we concluded that lncRNA-FTX plays a key role in the GSC-mediated malignant transformation of BMSCs in the glioma microenvironment, which is of great significance for further understanding the pathogenesis of glioma.

LINC00174 is a favorable prognostic biomarker in glioblastoma via promoting proliferative phenotype.

To investigate the expression pattern, prognostic value and biological functional of LINC00174 in glioma. In total, 140 glioma samples were collected as discovery cohort. TCGA RNA sequence dataset was obtained as validation set. Kaplan-Meier survival and multivariate Cox analysis were performed to evaluate survival difference. Furthermore, the biological function of LINC00174 was analyzed by clonogenic and intracranial tumor model assays. Overexpressed LINC00174 was significantly correlated with tumor grade as well as the higher mortality in survival analysis both in the discovery and the validation GBM cohorts. Besides, LINC00174 served as an independent prognostic indicator in glioblastoma patients. Additionally, knock down of LINC00174 expression significantly suppressed GBM cells' proliferation both in vitro and vivo. LINC00174 acts as an oncogene in glioma and may be a new potential therapeutic target.

LncRNA TTN‑AS1 upregulates RUNX1 to enhance glioma progression via sponging miR‑27b‑3p.

Long non-coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin-antisense RNA1 (TTN-AS1), miR-27b-3p and Runt-related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT-qPCR. Si-TTN-AS1 was transfected into glioma cell lines (U251 and LN229), and CCK-8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN-AS1 in glioma cells. miR-27b-3p inhibitor was used to explore the mechanisms. The results revealed that TTN-AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN-AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN-AS1 depletion in nude mice. Furthermore, we revealed that TTN-AS1 exerted oncogenic effects via sponging miR-27b-3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN-AS1 acts as an oncogene in glioma by targeting miR-27b-3p to release RUNX1. This finding may contribute to gene therapy of glioma.

Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1, by X.-L. Cui, X.-D. Wang, S.-K. Lin, C.-M. Miao, M. Wu, J.-G. Wei, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8449-8455-DOI: 10.26355/eurrev_201910_19157-PMID: 31646575" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19157.

ACYP2 contributes to malignant progression of glioma through promoting Ca2+ efflux and subsequently activating c-Myc and STAT3 signals

BackgroundAcylphosphatase 2 (ACYP2) is involved in cell differentiation, energy metabolism and hydrolysis of intracellular ion pump. It has been reported as a negative regulator in leukemia and a positive regulator in colon cancer, respectively. However, its biological role in glioma remains totally unclear.MethodsWe performed quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and western blot assays to evaluate ACYP2 expression. The functions of ACYP2 in glioma cells were determined by a series of in vitro and in vivo experiments, including cell proliferation, colony formation, cell cycle, apoptosis, migration, invasion and nude mouse tumorigenicity assays. In addition, western blot and co-immunoprecipitation (Co-IP) assays were used to identify its downstream targets.ResultsKnocking down ACYP2 in glioma cells significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Conversely, ectopic expression of ACYP2 in glioma cells dramatically promoted malignant phenotypes of glioma cells. Mechanistically, ACYP2 promoted malignant progression of glioma cells through regulating intracellular Ca2+ homeostasis via its interaction with PMCA4, thereby activating c-Myc and PTP1B/STAT3 signals. This could be effectively reversed by Ca2+ chelator BAPTA-AM or calpain inhibitor calpeptin.ConclusionsOur data demonstrate that ACYP2 functions as an oncogene in glioma through activating c-Myc and STAT3 signals via the regulation of intracellular Ca2+ homeostasis, and indicate that ACYP2 may be a potential therapeutic target and prognostic biomarker in gliomas.

Nur77 knock-down suppresses glioma by regulating CXCR4

IntroductionThe aim of this study is to explain the effects and mechanisms of Nur77 in glioma development.Material and methodsNur77 protein and gene expression were measured by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) in tissues from glioma and craniocerebral injury patients. The patients were divided into two groups according to median Nur77 gene expression and the correlations between clinical pathology, progression-free survival (PFS), overall survival (OS), and Nur77 gene expression were analysed. U257 and U87 cells were employed to assess the effects of Nur77 in cancer cell development by MTT, flow cytometry, and transwell and wound healing assays. Relative protein and gene expression were evaluated by Western blot assay and RT-qPCR, and PI3K nuclear volumes were evaluated by cellular immunofluorescence to explain the relevant mechanisms.ResultsCompared with that in normal tissues, Nur77 protein and gene expression in glioma tissues was significantly up-regulated (p &lt; 0.01); this up-regulation increased with increasing tumour stage (p &lt; 0.01). Compared with the high Nur77 expression group, the low Nur expression group showed significantly improved PFS and OS (both p &lt; 0.01). Nur77 gene expression appeared to be closely correlated with clinical pathology. In vitro studies of si-Nur77 transfection revealed a significant reduction in the cell viability of the si-Nur77 group, with increasing apoptosis rate (p &lt; 0.001). Nur77 knock-down resulted in significant downregulation of cell invasion and wound healing rates in the si-Nur77 group (p &lt; 0.01), with remarkable reductions in CXCR4 and PI3K.ConclusionsNur77 is an important oncogene in glioma, and Nur77 expression is closely correlated with glioma clinical pathology, PFS, and OS. Nur77 knock-down exerts inhibitory effects on glioma by regulating CXCR4/PI3K.

LncRNA LINC00665 Stabilized by TAF15 Impeded the Malignant Biological Behaviors of Glioma Cells via STAU1-Mediated mRNA Degradation

Glioma is a brain cancer characterized by strong invasiveness with limited treatment options and poor prognosis. Recently, dysregulation of long non-coding RNAs (lncRNAs) has emerged as an important component in cellular processes and tumorigenesis. In this study, we demonstrated that TATA-box binding protein associated factor 15 (TAF15) and long intergenic non-protein coding RNA 665 (LINC00665) were both downregulated in glioma tissues and cells. TAF15 overexpression enhanced the stability of LINC00665, inhibiting malignant biological behaviors of glioma cells. Both metal regulatory transcription factor 1 (MTF1) and YY2 transcription factor (YY2) showed high expression levels in glioma tissues and cells, and their knockdown inhibited malignant progression. Mechanistically, overexpression of LINC00665 was confirmed to destabilize MTF1 and YY2 mRNA by interacting with STAU1, and knockdown of STAU1 could rescue the MTF1 and YY2 mRNA degradation caused by LINC00665 overexpression. G2 and S-phase expressed 1 (GTSE1) was identified as an oncogene in glioma, and knockdown of MTF1 or YY2 decreased the mRNA and protein expression levels of GTSE1 through direct binding to the GTSE1 promoter region. Our study highlights a key role of the TAF15/LINC00665/MTF1(YY2)/GTSE1 axis in modulating the malignant biological behaviors of glioma cells, suggesting novel mechanisms by which lncRNAs affect STAU1-mediated mRNA stability, which can inform new molecular therapies for glioma.

Long non-coding RNA SNHG11 promotes cell proliferation, invasion and migration in glioma by targeting miR-154-5p.

Long non-coding RNAs (lncRNAs) play critical roles in tumour progression. However, the function of lncRNA small nucleolar RNA host gene 11 (SNHG11) in glioma has not been mentioned before. Our study aims to uncover the biological roles of SNHG11 in the progression of glioma and throw light for clinical treatment of glioma. The Gene Expression Profiling Interactive Analysis (GEPIA) dataset was used to analyze the SNHG11 expression between glioma and normal tissue, as well as survival benefit. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect SNHG11 and miR-154-5p expression. Celltiter-Glo, colony formation, and transwell assays were utilized to detect the influence of SNHG11 to the malignancy of U87 and U251 cells. The underlying pathways affected by SNHG11 were measured using Western blot. Furthermore, Luciferase reporter assay was applied to verify the interaction between SNHG11 and miR-154-5p. SNHG11 was upregulated in glioblastoma tissues and five malignant glioma cell lines. SNHG11 expression was negatively correlated with overall survival of glioma patients. Moreover, silencing of SNHG11 could decrease glioma cell viability both in vitro and in vivo. Furthermore, the inhibition of SNHG11 suppressed proliferation, invasion and migration via regulating epithelial-mesenchymal transition (EMT). In addition, SNHG11 could bind miRNA-154-5p and negatively regulate its level. SNHG11 functioned as an oncogene in glioma and promoted proliferation, invasion, and migration via EMT by sponging miR-154-5p. These findings provided a new therapeutic target for glioma.

LINC00662 sponges miR-107 accelerating the invasiveness and proliferation of glioma cells.

Increasing evidence revealed that the aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in tumorigenesis. However, the role and mechanisms of LINC00662 in glioma have not been elucidated. Here, we show that upregulation of LINC00662 expression in glioma is associated with advanced clinical features and poor prognosis. Our results from loss-of-function assays suggest that LINC00662 silencing suppresses the proliferative and invasive abilities of glioma cells. In vivo, glioma growth was inhibited by depletion of LINC00662 in nude mice. Mechanistically, LINC00662 directly interacts with miR-107. The High-mobility group box 1 protein (HMGB1) is a known target of miR-107. Moreover, rescue assays reveal that HMGB1 overexpression (or miR-107 inhibition) reverses the glioma growth inhibition caused by LINC00662 knockdown. In conclusion, our results indicate that LINC00662 acts as an oncogene in glioma by modulating the miR-107/HMGB1 axis, suggesting that LINC00662 could be a novel therapeutic target for glioma treatment.

MT1JP inhibits glioma progression via negative regulation of miR-24.

Long noncoding RNAs have been reported to be dysregulated and have pivotal roles in various human malignancies, including glioma. Previous studies revealed that metallothionein 1J (MT1JP) has important regulatory functions in the development of gastric cancer. However, the biological role and potential mechanism of MT1JP in glioma remain unknown. The present study suggested that MT1JP expression was significantly downregulated in glioma tissues and glioma cell lines, and the decreased expression of MT1JP was associated with glioma progression and poor survival of patients with glioma. Additionally, overexpression of MT1JP significantly inhibited the proliferation and invasion of glioma cells. Furthermore, it was revealed that MT1JP interacted with microRNA-24 (miR-24), which has previously been reported as an oncogene in glioma, negatively regulating its expression level. Rescue experiments revealed that the tumor suppressive functions of MT1JP may be mediated by the negative regulation of miR-24. Collectively, the data suggested that MT1JP inhibited the progression of glioma by negatively regulating miR-24 and may serve as a novel diagnostic biomarker and therapeutic target for glioma.

P62 acts as an oncogene and is targeted by miR-124-3p in glioma

BackgroundGlioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized.MethodsWe examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression.ResultsWe revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3′-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression.ConclusionsOur results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.

Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1.

The importance of circular RNAs in malignant tumors increases the attention of researchers. The role of circ_0067934 in glioma remains unclear. Our study aims to uncover how circ_0067934 functions in glioma development. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to determine the level of circ_0067934 in glioma tissues. Circ_0067934 was knocked down in glioma cells. Cell migrated and invaded ability was detected through functional assay in vitro and in vivo. Further mechanism assays were performed to explore the potential targets of circ_0067934. The circ_0067934 was highly expressed in glioma tissues compared with adjacent samples. The expression of circ_0067934 was upregulated in glioma cell lines. The cell migrated and invaded ability of glioma cells was inhibited after circ_0067934 was knocked down. Besides, CSF1 expression was decreased via knockdown of circ_0067934. Furthermore, tumor metastasis was inhibited after circ_0067934 was knocked down in nude mice. The circ_0067934 could suppress cell migration and invasion of glioma by upregulating CSF1.

Single-cell RNA-seq reveals RAD51AP1 as a potent mediator of EGFRvIII in human glioblastomas.

Recent advances in single-cell RNA sequencing (scRNA-seq) have endowed researchers with the ability to detect and analyze the transcriptomes of individual cancer cells. In the present study, 16,128 tumor cells from EGFR wild-type and EGFRvIII mutant cells were profiled by scRNA-seq. Analyses of scRNA-seq data from both U87MG and U87MG-EGFRvIII libraries revealed inherent heterogeneity in gene expression and biological processes. The cells stably expressing EGFRvIII showed enhanced transcriptional activities and a relatively homogeneous pattern, which manifested as less diverse distributions, gene expression levels and functional annotations compared with those of cells expressing the nonmutated version. Moreover, the differentially expressed genes between the U87MG and U87MG-EGFRvIII groups were mainly enriched in DNA replication, DNA repair and angiogenesis. We compared scRNA-seq data with bulk RNA-seq and EGFRvIII xenograft RNA-seq data. RAD51AP1 was shown to be upregulated in all three databases. Further analysis of RAD51AP1 revealed that it is an independent prognostic factor of glioma. Knocking down RAD51AP1 significantly inhibited tumor volume in an intracranial EGFRvIII-positive GBM model and prolonged survival time. Collectively, our microfluidic-based scRNA-seq driven by a single genetic event revealed a previously unappreciated implication of EGFRvIII in the heterogeneity of GBM and identified RAD51AP1 as an oncogene in glioma.

HOXC13-AS-miR-122-5p-SATB1-C-Myc feedback loop promotes migration, invasion and EMT process in glioma.

PurposeDifferentially expressed long non-coding ribonucleic acids (lncRNAs) have been reported as a key factor of glioma carcinogenesis, but the underlying mechanism involved is still unknown.Materials and methodsIn the present study, lncRNA HOXC13 antisense RNA (HOXC13-AS) was identified as a potential oncogene in glioma, and Western blotting, wound healing and Transwell assays were carried out to explore the effects of HOXC13-AS on the epithelial-mesenchymal transition (EMT) process as well as the migration and invasion of glioma cells.ResultsA further mechanistic study showed that HOXC13-AS sponged miR-122-5p to indirectly regulate SATB1 expression and affect the EMT process via the Wnt/β-catenin pathway. Meanwhile, the promoter activity was significantly increased via c-Myc, a key factor of the Wnt/β-catenin pathway, thus forming a positive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop to drive the malignant behavior in glioma.DiscussionThis study evidences the constitutive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop and provides a potential therapeutic target for glioma treatment.

A novel PTPRZ1-ETV1 fusion in gliomas.

The aggressive nature of malignant gliomas and their genetic and clinical heterogeneity present a major challenge in their diagnosis and treatment. Development of targeted therapy brought attention on detecting novel gene fusions, since they represent promising therapeutic targets (eg, TRK inhibitors in NTRK fusion-positive tumors). Using targeted next-generation sequencing, we prospectively analyzed 205 primary brain tumors and detected a novel PTPRZ1-ETV1 fusion transcript in 11 of 191 (5.8%) gliomas, including nine glioblastomas, one anaplastic oligodendroglioma and one pilocytic astrocytoma. PTPRZ1-ETV1 fusion was confirmed by RT-PCR followed by Sanger sequencing, and in-silico analysis predicted a potential driver role. The newly detected fusion consists of the PTPRZ1 promoter in frame with the highly conserved DNA-binding domain of ETV1 transcription factor. The ETV1 and PTPRZ1 genes are known oncogenes, involved in processes of tumor development. ETV1 is a member of the ETS family of transcription factors, already known oncogenic drivers in Ewing sarcoma, prostate cancer and gastrointestinal stromal tumors, but not in gliomas. Its overexpression contributes to tumor growth and more aggressive tumor behavior. PTPRZ1 is already considered to be a tumor growth promoting oncogene in gliomas. In 8%-16% of gliomas, PTPRZ1 is fused to the MET oncogene, resulting in a PTPRZ1-MET fusion, which is associated with poorer prognosis but is also a positive predictive biomarker for treatment with kinase inhibitors. In view of the oncogenic role that the two fusion partners, PTPRZ1 and ETV1, exhibit in other malignancies, PTPRZ1-ETV1 fusion might present a novel potential therapeutic target in gliomas. Although histopathological examination of PTPRZ1-ETV1 fusion-positive gliomas did not reveal any specific or unique pathological features, and the follow-up period was too short to assess prognostic value of the fusion, careful monitoring of patients and their response to therapy might provide additional insights into the prognostic and predictive value of this novel fusion.

PAX3 Promotes Proliferation of Human Glioma Cells by WNT/β-Catenin Signaling Pathways.

The PAX3 (paired box 3) gene plays an important role in embryonic development, diseases, and cancer formation. Our preliminary studies have shown that PAX3 gene is upregulated in glioma cells, which is associated with a worse prognosis. Moreover, PAX3, by facilitating cell proliferation and invasion and inhibiting cell apoptosis, plays an oncogenic role in glioma. However, the specific molecular mechanism of PAX3 acting as an oncogene in glioma remains unclarified. In the present study, we have found that PAX3 overexpression was observed in high grade glioma and predicted a worse prognosis. PAX3 overexpression did not correlate significantly to IDH1 mutation and MGMT methylation. Moreover, the expression of PAX3 was positively correlated with that of β-catenin. In U87 glioma cells, PAX3 interacted with β-catenin, as was confirmed by CO-IP. Besides, PAX3 overexpression promoted cell proliferation and cell cycle progression, while it inhibited cell apoptosis by altering the expressions of important molecules associated with the Wnt signaling pathway, including β-catenin, Myc, VEGF, cyclinD1, MMP7, and Wnt1. In the meantime, it was also proved that PAX3 correlated to β-catenin through a negative regulatory mechanism with respect to the promotion of U87 glioma cell proliferation and cell cycle progression and inhibition of the cell apoptosis. Our experiment demonstrated the role of PAX3 in promoting glioma growth and development, possibly by interacting directly with β-catenin and regulating the Wnt signaling pathway.