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)

Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR-424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas.
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PMID:Knockdown of lncRNA PVT1 Inhibits Glioma Progression by Regulating miR-424 Expression. 3083 54

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.
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PMID:NOB1: A Potential Biomarker or Target in Cancer. 3085 59

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

MicroRNAs (miRs) play important roles in tumor progression. miR-936 has been reported to suppress cell invasion and proliferation of glioma and non-small cell lung cancer. Nevertheless, the function of miR-936 in laryngeal squamous cell carcinoma (LSCC) remains undiscovered. Hence, our study was to investigate the role of miR-936 in LSCC. In our present research, we have testified that miR-936 was substantially downregulated in LSCC tissues compared with adjacent normal tissues. Furthermore, miR-936 could inhibit proliferation, migration and invasion, and improve the sensitivity to doxorubicin and cisplatin of LSCC cells. Additionally, luciferase reporter assays were performed to confirm that GPR78 was a novel target of miR-936, and the protein expression of GPR78 was obviously inhibited by miR-936 in LSCC cells. In summary, our study indicates that the miR-936/GPR78 axis could be both a diagnostic marker and a therapeutic target for LSCC.
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PMID:miR-936 Suppresses Cell Proliferation, Invasion, and Drug Resistance of Laryngeal Squamous Cell Carcinoma and Targets GPR78. 3211 23

Although angiogenesis inhibitors targeting VEGF/VEGFR2 have been applied for tumor therapy, the outcomes are still unsatisfactory. Thus, it is urgent to develop novel angiogenesis inhibitor for cancer therapy from new perspectives. Identification of novel angiogenesis inhibitor from natural products is believed to be one of most promising strategy. In this study, we showed that pristimerin, an active agent isolated from traditional Chinese herbal medicine Celastrus aculeatus Merr, was a novel tumor angiogenesis inhibitor that targeting sonic hedgehog (Shh)/glioma associated oncogene 1 (Gli1) signaling pathway in non-small cell lung cancer (NSCLC). We showed that pristimerin affected both the early- and late-stage of angiogenesis, suggesting by that pristimerin inhibited Shh-induced endothelial cells proliferation, migration, invasion as well as pericytes recruitment to the endothelial tubes, which is critical for the new blood vessel maturation. It also suppressed tube formation, vessel sprouts formation and neovascularization in chicken embryo chorioallantoic membrane (CAM). Moreover, it significantly decreased microvessel density (MVD) and pericyte coverage in NCI-H1299 xenografts, resulting in tumor growth inhibition. Further research revealed that pristimerin suppressed tumor angiogenesis by inhibiting the nucleus distribution of Gli1, leading to inactivation of Shh/Gli1 and its downstream signaling pathway. Taken together, our study showed that pristimerin was a promising novel anti-angiogenic agent for the NSCLC therapy and targeting Shh/Gli1 signaling pathway was an effective approach to suppress tumor angiogenesis.
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PMID:Identification of a novel tumor angiogenesis inhibitor targeting Shh/Gli1 signaling pathway in Non-small cell lung cancer. 3228 74

The long non-coding RNA (lncRNA) GAS8-AS1 is the second-most frequently altered gene, following the BRAF gene, in papillary thyroid carcinoma (PTC). We aimed to study the specificity and significance of genetic alterations in GAS8-AS1 in PTC. In this study, we reported the prevalence of genetic alterations of GAS8-AS1 in tissues of 48 nodular goiter, 573 papillary thyroid cancer, 95 colorectal cancer, 101 non-small cell lung cancer, 92 glioma, and 69 gastrointestinal stromal tumor patients, and in peripheral white blood cells of 286 healthy volunteers. We observed that the genomic sequence of GAS8-AS1 had a high frequency of genetic alterations in addition to the previously reported c.713A>G/714T>C substitution. Substitution of c.713A>G was completely linked with four other loci at c.714T>C, c.728A>G, c.737G>A, and c.752G>A. Two novel substitutions at c.749G>A and c.826A>G were also found. Interestingly, evidence from different samples indicated that these variations were not unique variants for PTC; they were also found in other malignant tissues and white blood cells of healthy volunteers. The c.713A>G substitution was associated with the T stage of PTC, while c.749G>A was more likely to occur in younger patients with PTC. PTC patients carrying heterozygous variants at the c.749 and c.826 loci had a higher risk of developing multiple lesions. These associations were also observed in patients with PTC and concomitant benign thyroid disease. Notably, the rare homozygous GG at the c.826 site conferred a higher risk of developing T2 PTC without benign thyroid disease, and a lower risk of developing T2 PTC with benign thyroid disease. Alterations of c.749G>A and c.826A>G had higher levels of serum TSH (thyroid stimulating hormone) in PTC subjects. Our study provides evidence that the detection of GAS8-AS1 genetic alterations would be useful in diagnostic screening and prognostic assessment of PTC.
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PMID:lncRNA GAS8-AS1 genetic alterations in papillary thyroid carcinoma and their clinical significance. 3267 93

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

Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non-small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial-mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance. We developed two novel series of CD73 antibody, Ab001/Ab002 and humanized version Hu001/Hu002, which demonstrated high CD73 binding affinity, potent enzyme inhibition, and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Hu001/Hu002 inhibited growth of RAS-mutant NSCLC tumors in mice via enhanced antibody-dependent cell-mediated cytotoxicity and multifaceted remodeling of the tumor immune environment, reflecting diminished levels of tumor-associated macrophages, myeloid-derived suppressor cells, and tumor vasculature. A novel MMAE-conjugated CD73-ADC (Hu001-MMAE) elicited potent cytotoxicity against CD73-high expressing tumor cells (IC50<0.1 nmol/L) and suppressed in vivo growth of multiple NSCLC and glioma tumors, including the RAS-mutant models [minimum effective dose <1 mg/kg]. Treatment with CD73-ADC triggered a robust intratumoral accumulation of proinflammatory macrophages and activated dendritic cells (DC), which were not observed with naked CD73 antibody or standard chemotherapy. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer.
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PMID:Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody-Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function. 3294 46

Sirtuin 2 (SIRT2) is a member of the sirtuin protein family. It is a Class III histone deacetylase (HDACs) and predominantly localized to the cytosol. SIRT2 deacetylates histones and a number of non-histone proteins and plays a pivotal role in various physiologic processes. Previously, SIRT2 has been considered indispensable during carcinogenesis; however, there is now a significant controversy regarding whether SIRT2 is an oncogene or a tumor suppressor. The purpose of this review is to summarize the physiological functions of SIRT2 and its mechanisms in cancer. We will focus on five malignancies (breast cancer, non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, and glioma) to describe the current status of SIRT2 research and discuss the clinical evaluation of SIRT2 expression and the use of SIRT2 inhibitors.
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PMID:The Clinical Significance of SIRT2 in Malignancies: A Tumor Suppressor or an Oncogene? 3301 52

Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.
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PMID:MicroRNA-936/ERBB4/Akt axis exhibits anticancer properties of gastric cancer through inhibition of cell proliferation, migration, and invasion. 3302 Oct 20


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