scholarly journals Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769457 ◽  
Author(s):  
Ryuk-Jun Kwon ◽  
Myoung-Eun Han ◽  
Youn-Jae Kim ◽  
Yun Hak Kim ◽  
Ji-young Kim ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Zinc Fingers ◽  
In Silico Analysis ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Glioblastoma Cells ◽  
Protein Expressions ◽  
Immunohistochemical Studies ◽  
Prognostic Maker

Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients’ tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival. In vitro, the downregulation of ZHX1 decreased the proliferation, migration, and invasion of glioblastoma cells, whereas its upregulation had the opposite effects. In addition, we showed ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2. Taken together, this study demonstrates that ZHX1 plays crucial roles in the progression of glioblastoma, and its findings suggest that ZHX1 be viewed as a potential prognostic maker and therapeutic target of glioblastoma.

scholarly journals MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769167 ◽  
Author(s):  
Ju Guo ◽  
Runfu Cao ◽  
Xingwei Yu ◽  
Zewen Xiao ◽  
Zhiwen Chen
Keyword(s):  
Nuclear Receptor ◽  
Bladder Carcinoma ◽  
Messenger Rna ◽  
Tumor Tissue ◽  
Protein Translation ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Nuclear Receptor Coactivator ◽  
Bladder Carcinoma Cells

The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3′-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.

scholarly journals Fermented Mistletoe Extract as a Multimodal Antitumoral Agent in Gliomas

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Oliver Podlech ◽  
Patrick N. Harter ◽  
Michel Mittelbronn ◽  
Simone Pöschel ◽  
Ulrike Naumann
Keyword(s):  
Immune Cell ◽  
Nk Cell ◽  
Migration And Invasion ◽  
Immunomodulatory Activity ◽  
Concomitant Treatment ◽  
Glioblastoma Cells ◽  
Active Components ◽  
Mistletoe Extract ◽  
Positive Effects

In Europe, commercially available extracts from the white-berry mistletoe (Viscum albumL.) are widely used as a complementary cancer therapy. Mistletoe lectins have been identified as main active components and exhibit cytotoxic effects as well as immunomodulatory activity. Since it is still not elucidated in detail how mistle toe extracts such as ISCADOR communicate their effects, we analyzed the mechanisms that might be responsible for their antitumoral function on a molecular and functional level. ISCADOR-treated glioblastoma (GBM) cells down-regulate central genes involved in glioblastoma progression and malignancy such as the cytokine TGF-βand matrix-metalloproteinases. Usingin vitroglioblastoma/immune cell co-cultivation assays as well as measurement of cell migration and invasion, we could demonstrate that in glioblastoma cells, lectin-rich ISCADOR M and ISCADOR Q significantly enforce NK-cell-mediated GBM cell lysis. Beside its immune stimulatory effect, ISCADOR reduces the migratory and invasive potential of glioblastoma cells. In a syngeneic as well as in a xenograft glioblastoma mouse model, both pretreatment of tumor cells and intratumoral therapy of subcutaneously growing glioblastoma cells with ISCADOR Q showed delayed tumor growth. In conclusion, ISCADOR Q, showing multiple positive effects in the treatment of glioblastoma, may be a candidate for concomitant treatment of this cancer.

scholarly journals Knockdown of Ezrin inhibited migration and invasion of cervical cancer cells in vitro

2020 ◽  
Vol 34 ◽  
pp. 205873842093089
Author(s):  
Meili Xi ◽  
Wenbin Tang
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Messenger Rna ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Sulforhodamine B ◽  
Ezrin Expression ◽  
Cervical Cancer Cells ◽  
Polymerase Chain

Cervical cancer is the fourth most common malignancy in women. The aim of this study was to investigate the functions of Ezrin in cervical cancer cells. Two cervical cancer cell lines, SiHa and CaSki, were cultured in vitro. Following the knockdown of Ezrin using siRNA, real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were applied to analyze Ezrin expression at the messenger RNA (mRNA) and protein levels. Subsequently, wound healing assay, transwell assay, and sulforhodamine B (SRB) assay were used to detect the migration, invasion, and viability of cervical cancer cells, respectively. Results revealed that Ezrin siRNA can notably inhibit the migration and invasion of SiHa and CaSki cells ( P  < 0.05). However, knockdown of Ezrin shows no effects on the viability of SiHa and CaSki cells ( P  < 0.05). It is indicated that Ezrin plays a possible role in promoting the migration and invasion of cervical cancer cells and may be a therapeutic target to prevent metastasis of cervical cancer.

scholarly journals Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

2013 ◽  
Vol 319 (13) ◽  
pp. 2037-2048 ◽  
Author(s):  
Eva Bernhart ◽  
Sabine Damm ◽  
Andrea Wintersperger ◽  
Trevor DeVaney ◽  
Andreas Zimmer ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Migration And Invasion ◽  
Glioblastoma Cells

scholarly journals Upregulation of Interleukin 8 by Oxygen-deprived Cells in Glioblastoma Suggests a Role in Leukocyte Activation, Chemotaxis, and Angiogenesis

1997 ◽  
Vol 186 (8) ◽  
pp. 1201-1212 ◽  
Author(s):  
Isabelle Desbaillets ◽  
Annie-Claire Diserens ◽  
Nicolas de Tribolet ◽  
Marie-France Hamou ◽  
Erwin G.  Van Meir
Keyword(s):  
Messenger Rna ◽  
Chemokine Receptors ◽  
Pcr Analysis ◽  
Low Grade ◽  
Normal Brain ◽  
Leukocyte Infiltration ◽  
Reverse Transcription Pcr ◽  
Biological Phenomena ◽  
Inflammatory Stimuli

Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8–binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8–binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2.

scholarly journals Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hua-fu Zhao ◽  
Chang-peng Wu ◽  
Xiu-ming Zhou ◽  
Peng-yu Diao ◽  
Yan-wen Xu ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Nude Mice ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Combination Strategy ◽  
Combination Effects

Abstract Background Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110β (PI3Kβ) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kβ. Methods To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient’s specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kβ inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated. Results MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients’ specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kβ and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin. Conclusion Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kβ and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.

scholarly journals MCP-1 and MIP-3α Secreted from Necrotic Cell-Treated Glioblastoma Cells Promote Migration/Infiltration of Microglia

2018 ◽  
Vol 48 (3) ◽  
pp. 1332-1346 ◽  
Author(s):  
Yieun Jung ◽  
So-Hee Ahn ◽  
Hyunju Park ◽  
Sang Hui Park ◽  
Kyungsun Choi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Primary Brain Tumor ◽  
Brain Parenchyma ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Glioblastoma Cells ◽  
Mobility Shift ◽  
Diffuse Infiltration ◽  
Nuclear Extracts ◽  
Mrna And Protein Expression

Background/Aims: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The defining characteristics of GBM are diffuse infiltration of tumor cells into normal brain parenchyma, rapid growth, a high degree of infiltration of microglia and macrophages, and the presence of necrosis. Microglia/macrophages are frequently found in gliomas and they extensively infiltrate GBM tissue, up to 30% of total tumor mass. However, little is known about the effect of necrotic cells (NCs) on microglia infiltration in GBM and the tumor-infiltrating microglia-induced factors in GBMs. Methods: In this study, to address whether necrosis or necrosis-exposed GBM cells affect the degree of microglia/macrophage infiltration, migration and invasion/infiltration assays were performed. Culture supernatants and nuclear extracts of CRT-MG cells treated or untreated with necrotic cells were analyzed using a chemokine array and electrophoretic mobility shift assay, respectively. Results: The presence of NCs promoted the migration/infiltration of microglia, and GBM cell line CRT-MG cells exposed to NCs further enhanced the migration and infiltration of HMO6 microglial cells. Treatment with NCs induced mRNA and protein expression of chemokines such as <unterline>M</unterline>onocyte <unterline>C</unterline>hemoattractant <unterline>P</unterline>rotein-1 (CCL2/MCP-1) and <unterline>M</unterline>acrophage <unterline>I</unterline>nflammatory <unterline>P</unterline>rotein-3α (CCL20/MIP-3α) in CRT-MG cells. In particular, CCL2/MCP-1 and CCL20/MIP-3α were significantly increased in NC-treated CRT-MG cells. NCs induced DNA binding of the transcription factors <unterline>N</unterline>uclear <unterline>F</unterline>actor (NF)-κB and <unterline>A</unterline>ctivator <unterline>P</unterline>rotein 1 (AP-1) to the CCL2/MCP-1 and CCL20/MIP-3α promoters, leading to increased CCL2/MCP-1 and CCL20/MIP-3α mRNA and protein expression in CRT-MG cells. Conclusion: These results provide evidence that NCs induce the expression of CCL2/MCP-1 and CCL20/MIP-3α in glioblastoma cells through activation of NF-κB and AP-1 and facilitate the infiltration of microglia into tumor tissues.

scholarly journals LINC00675 is a prognostic factor and regulates cell proliferation, migration and invasion in glioma

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Zhibing Li ◽  
Yijian Li ◽  
Qibai Wang
Keyword(s):  
Cell Proliferation ◽  
Cancer Colorectal ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Large Tumor ◽  
Who Grade ◽  
Protein Expressions ◽  
Glioma Cell Proliferation ◽  
Expression Status

LINC00675 has been suggested to be dysregulated in gastric cancer, colorectal cancer and pancreatic cancer. However, the expression status and biological function of LINC00675 in glioma were still unknown. Thus, we reported LINC00675 was overexpressed in glioma tissues and cell lines, and positively associated with advanced WHO grade, large tumor size and poor prognosis. Moreover, univariate and multivariate analyses suggested that high-expression of LINC00675 was an independent unfavorable prognostic predictor for glioma. In addition, levels of LINC00675 expression were positively correlated with TRIP6 mRNA and protein expressions. The in vitro experiment showed that silencing of LINC00675 inhibits glioma cell proliferation, migration and invasion through regulating TRIP6. In conclusion, LINC00675 acts as a tumor promoter in glioma progression.

scholarly journals miR-517a is up-regulated in glioma and promotes glioma tumorigenesis in vitro and in vivo

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng-li Du ◽  
Fei Peng ◽  
Ke-qin Liu
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Functional Assay ◽  
Normal Brain ◽  
Pathology Classification ◽  
The Status ◽  
Induced Apoptosis

Abstract miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo. Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR–517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

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