Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway is important in the regulation of cell proliferation through its production of phosphatidylinositol 3,4,5-triphosphate (PIP3). Activation of this pathway is frequently observed in human cancers, including non-small cell lung carcinoma. The PI3-K/Akt pathway is negatively regulated by the dual-specificity phosphatase and tensin homolog (PTEN) protein. PTEN acts as a direct antagonist of PI3-K by dephosphorylating PIP3. Studies have shown that PTEN phosphatase activity is inhibited by PREX2, a guanine nucleotide exchanger factor (GEF). Multiple studies revealed that CELF2, an RNA binding protein, cooperates synergistically with PTEN as a tumor suppressor in multiple cancers. However, the underlying mechanism as to how CELF2 enhances PTEN activity remains unclear. Here, we report that CELF2 interacts with PREX2 and reduces the association of PREX2 with PTEN. Consistent with this observation, PTEN phosphatase activity is upregulated with CELF2 overexpression. In addition, overexpression of CELF2 represses both Akt phosphorylation and cell proliferation only in the presence of PTEN. In an ex vivo study, CELF2 gene delivery could significantly inhibit patient-derived xenografts (PDX) tumor growth. To further investigate the clinical relevance of this finding, we analyzed 87 paired clinical lung adenocarcinoma samples and the results showed that CELF2 protein expression is downregulated in tumor tissues and associated with poor prognosis. The CELF2 gene is located on the chromosome 10p arm, a region frequently lost in human cancers, including breast invasive carcinoma, low-grade glioma and glioblastoma. Analysis of TCGA datasets showed that CELF2 expression is also associated with shorter patient survival time in all these cancers. Overall, our work suggests that CELF2 plays a novel role in PI3-K signaling by antagonizing the oncogenic effect of PREX2.
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PMID:CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction. 3124 Nov 30

Anoikis is a specific form of programmed cell death induced by loss of contact between cells and extracellular matrices or other cells. Only tumor cells that are resistant to anoikis can survive in the state of detachment from the primary tissue during the early stages of metastasis. The ability to resist anoikis is crucial for cancer cell metastasis. ILF2 is a proto-oncogene previously studied in glioma, NSCLC, esophageal cancer and pancreatic ductal carcinoma. The results from the present study revealed that the transcription factor interleukin enhancer-binding factor 2 (ILF2) was highly expressed in non-small cell lung cancer (NSCLC) cell lines compared with in normal cell lines. ChIP and luciferase reporter gene assays demonstrated that ILF2 inhibited the expression level of the tumor suppressor gene phosphatase and tensin homolog (PTEN) by directly binding to its upstream regulatory region. Furthermore, the results from the detection of cell adhesion and apoptosis in cell suspension culture demonstrated that this mechanism enabled NSCLC cells to reduce adherence to the matrix and to survive in this abnormal state. These results suggested that ILF2 may promote the anchorage-independence of NSCLC cells through the suppression of PTEN.
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PMID:ILF2 promotes anchorage independence through direct regulation of PTEN. 3142 36

Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.
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PMID:Brain Tumors of Glial Origin. 3176 Jun 51

A recent study reported that zinc finger protein (ZNF)281 is a tumor-suppressive long non-coding (lnc)RNA in glioma. The present study investigated the role of ZNF281 in non-small cell lung cancer (NSCLC). ZNF281 expression in paired cancer and non-cancerous tissues from patients with NSCLCs was analyzed by RNA extraction and reverse transcription-quantitative-PCR. A 5-year follow up on patients was performed to analyze the prognostic value of ZNF281 for NSCLC. Cell transfections of ZNF281 or phosphatase and tensin homolog (PTEN) expression vector and microRNA (miR)-221 mimic were performed to analyze the relationship between ZNF281, miR-221 and PTEN. Cell apoptosis and proliferation were analyzed using Cell Counting Kit-8 and flow cytometry, respectively. In patients with NSCLC, expression levels of ZNF281 were significantly lower in cancer tissues compared with in non-cancerous tissues, and lower levels of ZNF281 expression in cancerous tissues predicted poor survival. In NSCLC cells, ZNF281 overexpression resulted in upregulated PTEN and downregulated miR-221 expression, whereas cells with miR-221 overexpression exhibited downregulated PTEN expression and unaffected ZNF281 expression. In addition, ZNF281 and PTEN overexpression resulted in accelerated cell apoptosis and inhibited the cell proliferation of NSCLC cells. Notably, miR-221 overexpression exhibited an opposite effect and attenuated the functions of ZNF281 and PTEN overexpression. Therefore, ZNF281 may upregulate PTEN via downregulation of miR-221 in NSCLC, resulting in inhibition of cancer cell proliferation and the promotion of apoptosis.
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PMID:Long non-coding RNA-ZNF281 upregulates PTEN expression via downregulation of microRNA-221 in non-small cell lung cancer. 3278 13

Recently, the role of long noncoding RNA (lncRNA) has been identified in human diseases, and we aim to explore the role of lncRNA antidifferentiation noncoding RNA (ANCR) in glioma. Expression of lncRNA ANCR, enhancer of zeste homolog 2 (EZH2), and phosphatase and tensin homolog (PTEN) in glioma tissues and cells was determined by RT-PCR or western blot assay. The correlation between expression of ANCR, EZH2, and PTEN in glioma tissues was analyzed using Pearson test. The apoptosis, transwell invasion, migration, colony formation, and proliferation assays were conducted to evaluate the influences of lncRNA ANCR depletion, EZH2 reduction, or PTEN elevation on the cell biology of glioma cells. The relationships between ANCR and EZH2, and between EZH2 and PTEN were confirmed through RIP, RNA pull-down, and chromatin immunoprecipitation assays. Our results indicated that ANCR and EZH2 were upregulated and PTEN was downregulated in glioma tissues and cell lines. ANCR expression was positively related to EZH2 expression, while PTEN expression was negatively related to ANCR/EZH2 expression. Inhibited ANCR, reduced EZH2, or elevated PTEN could reduce the ability of invasion, migration, and proliferation, and promote apoptosis of glioma cells. PTEN overexpression or EZH2 inhibition reversed the promotive role of ANCR upregulation in glioma cell growth and metastasis. Mechanistically, PTEN was upregulated in ANCR knockdown glioma cells. EZH2 interacted with ANCR in glioma cells. In conclusion, we have found that restrained ANCR could repress invasion, migration, and proliferation, as well as promote apoptosis of glioma cells through interacting with EZH2 and regulating the expression of PTEN, offering an effective therapeutic target for patients with glioma.
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PMID:LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression. 3329 63


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