Zinc Finger E-Box Binding Homeobox 1 Regulates the Biological Behavior of Glioma Cells via iNOS/NF-κB Signaling

2021 ◽  
Vol 11 (2) ◽  
pp. 333-338
Author(s):  
Jing Cao ◽  
Haiyan Zhou ◽  
Fan Yang ◽  
Duojiao Fan ◽  
Hengzhou Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Clinicopathological Characteristics ◽  
Biological Behavior ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Tumor Group ◽  
Inhibit Cell Proliferation ◽  
E Cadherin

The gliomas pathogenesis is complex and effective molecular targets are still unclear. ZEB1 regulates epithelial mesenchymal transition (EMT) and participates in tumors. Our study intends to analyze ZEB1’s role in glioma cells. qRT-PCR detected ZEB1 mRNA expression in normal group and tumor group. ZEB1 siRNA was transfected into glioma cells followed by measuring ZEB1, E-cadherin and Vimentin expression, cell proliferation, Capase-3 activity as well as NF-κB and iNOS changes by immunoblotting. Upregulation of ZEB1 was found in glioma tumor tissue and correlated with glioma clinicopathological characteristics. Interfering with ZEB1 by siRNA significantly down-regulated ZEB1, inhibited cell proliferation, increased Capase-3 activity, down regulated NF-κB and iNOS proteins in glioma cells, elevated E-cadherin and decreased Vimentin level (P <0.05). ZEB1 down regulation in glioma cells can change the expression of NF-κB/iNOS, regulate cell apoptosis and inhibit cell proliferation, thereby delaying EMT process.

miR-16 Inhibits Extracellular Signal-Regulated Kinases (ERK) Mitogen-Activated Protein Kinases (MAPK) Signaling to Affect Epithelial-Mesenchymal Transition (EMT) and Invasion of Glioma Cells

2022 ◽  
Vol 12 (4) ◽  
pp. 848-853
Author(s):  
Peng Sun ◽  
Duojiao Fan ◽  
Jing Cao ◽  
Haiyan Zhou ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Mapk Signaling ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
U251 Cells ◽  
E Cadherin

Abnormal MEK1 expression is associated with tumor cell EMT, invasion and metastasis. Decreased miR-16 level is associated with glioma. Bioinformatics analysis showed a relationship between miR-16 and MEK1. This study assessed whether miR-16 regulates MEK1 expression and affects glioma cell EMT and invasion. The tumor tissues and adjacent glioma tissues were collected to measure miR-16 and MEK1 mRNA. The dual luciferase assay validated the relation of miR-16 with MEK1. U251 cells were cultured and assigned into NC group and mimic group, followed by analysis of cell biological behaviors, and MEK1, p-ERK1/2, E-cadherin, N-Cadherin expression. Compared with adjacent tissues, miR-16 expression was significantly decreased and MEK1 was elevated in glioma tissues. Compared with HEB, miR-16 in glioma U251 and SHG44 cells was decreased and MEK1 was increased. Dual luciferase reporter gene experiments confirmed the relation of miR-16 with MEK1. Transfection of miR-16 mimic significantly down-regulated MEK1, p-ERK1/2 and N-cadherin in U251 cells, upregulated E-cadherin, inhibited cell proliferation, promoted apoptosis, and attenuated EMT and invasion of glioma cells. In conclusion, decreased miR-16 expression and increased MEK1 expression is related to glioma pathogenesis. Overexpression of miR-16 can inhibit MEK1 expression, ERK/MAPK signaling, glioma cell proliferation, promote apoptosis, and attenuate EMT and invasion.

scholarly journals Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 921-931
Author(s):  
Juan Zhao ◽  
Xue-Bin Zeng ◽  
Hong-Yan Zhang ◽  
Jie-Wei Xiang ◽  
Yu-Song Liu
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractLong non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

scholarly journals Tumor-Suppressive Function of lncRNA-MEG3 in Glioma Cells by Regulating miR-6088/SMARCB1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Gong ◽  
Meng-Yi Huang
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Favorable Effect ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
And Migration ◽  
Proliferation And Migration ◽  
Glioma Progression

Objective. Mounting evidence has elaborated the implication of long noncoding RNAs (lncRNAs) in tumorigenesis of several cancers, including glioma. However, little was known about the mechanism of lncRNA maternally expressed gene 3 (MEG3) in the development and progression of glioma. This work is designed to explore the effect of MEG3 on glioma progression and its possible mechanism. Methods. Expressions of lncRNA-MEG3 and SMARCB1 were detected in human glioblastoma U87 and U251 cell lines. Gain and loss of function of MEG3 or/and miR-6088 was performed in U87 and U251 cells to observe its effect on cell proliferation and migration as well as on epithelial-mesenchymal transition (EMT) related markers. Luciferase reporter gene assay was employed to inspect the interactions among MEG3, miR-6088, and SMARCB1. Results. MEG3 and SMARCB1 expressions were downregulated in glioma cells. Transfection of pcDNA3.1-MEG3 or pcDNA3.1-SMARCB1 plasmids could clearly block cell proliferation, migration, and EMT progression. MEG3 functions as a sponge for miR-6088, while SMARCB1 is a downstream protein of miR-6088. Transfection of miR-6088 mimic or si-SMARCB1 could obviously reverse the favorable effect of pcDNA3.1-MEG3 on glioma progression. Conclusion. Collectively, the evidence in this study indicated that MEG3 was downregulated in glioma cells and inhibited proliferation and migration of glioma cells via regulating miR-6088/SMARCB1 axis.

LncRNA CEACAMP8 Regulates the Proliferation, Invasion and Migration of Trophoblast Cells

2019 ◽  
Vol 9 (9) ◽  
pp. 1215-1221
Author(s):  
Li Jie ◽  
Zhangcai Zheng ◽  
Liping Liu ◽  
Yali Liu ◽  
Zhaoyan Meng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Flow Cytometry Analysis ◽  
Trophoblast Cells ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Qpcr Analysis ◽  
And Migration ◽  
E Cadherin

Preeclampsia (PE) is an idiopathic hypertension syndrome occurring after 20 weeks of gestation. Reports showed that lncRNAs expression was abnormal in preeclampsia. We aimed to investigate the role of lncRNA CEACAMP8 in the proliferation, invasion and migration of trophoblast cells to improve the preeclampsia. The cell transfection effects were determined by RT-qPCR analysis. The proliferation, invasion and migration of HTR-8/SVneo cells were detected by CCK-8 assay, transwell assay and wound healing assay. The flow cytometry analysis analyzed the cell cycle. Moreover, the expression of CDK2, cyclinD1, P21, MMP2, MMP9, E-cadherin, b-catenin and vimentin was determined by the western blot analysis. Consequently, CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and kept most of the cells in the S phase. The expression of proteins related to the proliferation, invasion and migration of HTR-8/SVneo cells were also changed in accordance with the increase of proliferation, invasion and migration of HTR-8/SVneo cells. In addition, lncRNA CEACAMP8 inhibition decreased the expression of E-cadherin and b-catenin, and increased the vimentin expression to promote the epithelial-mesenchymal transition. And, CEACAMP8 overexpression could reverse the above changes. This study indicated that CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and lncRNA CEACAMP8 overexpression reversed.

scholarly journals Clinical significance of epithelial–mesenchymal transition–related molecules in lung adenocarcinoma

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
Y. Zhang ◽  
L. F. Wang ◽  
J. H. Gao ◽  
L. Li ◽  
P. Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumour ◽  
Smoking History ◽  
Related Protein ◽  
Vimentin Expression ◽  
Clinicopathologic Characteristics ◽  
Mesenchymal Transition ◽  
The Relationship ◽  
E Cadherin

Background Epithelial–mesenchymal transition (emt) refers to the biologic process in which epithelial cells are transformed into interstitial phenotypes by specific pathways. This transition plays an important biologic role in the process by which epithelium-derived malignant tumour cells acquire the ability to migrate and invade. We explored the relationship between emt-associated molecules and patient-related clinical factors to determine whether any clinical characteristics could be used as biomarkers for emt-related protein alterations in lung cancer—especially lung adenocarcinoma.Methods Tumour specimens were collected from 80 patients with lung adenocarcinoma who underwent surgery or lung biopsy, with 4 patients being evaluated a 2nd time after re-biopsy. Expression of emt-related proteins, including E-cadherin and vimentin, was evaluated by immunohistochemistry. We analyzed the relationship between clinicopathologic characteristics and expression level of the emt markers.Results Positive expression of E-cadherin was observed in 63 patients (79%), and vimentin, in 46 patients (57.5%). No significant relationships between E-cadherin or vimentin expression and smoking history, sex, age, driving gene mutations, or cell differentiation were identified. A significant correlation was observed between vimentin expression and pathologic stage. Of the 4 patients who were evaluated a 2nd time after re-biopsy, 3 showed the same emt-related protein expression status as in the first analysis. In the remaining patient, E-cadherin had changed completely.Conclusions Clinicopathologic factors in cancer patients did not help to diagnose emt status in lung adenocarcinoma; however, TNM stage might be associated with vimentin expression.

scholarly journals Post-translational modifications of EMT transcriptional factors in cancer metastasis

2016 ◽  
Vol 11 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Rui Chang ◽  
Peng Zhang ◽  
Jiacong You
Keyword(s):  
Protein Modification ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Transcriptional Factors ◽  
Protein Stabilization ◽  
Biological Behavior ◽  
Post Translational Modifications ◽  
Mesenchymal Transition ◽  
Substrate Proteins ◽  
E Cadherin

AbstractMetastasis is an important reason for death of cancer patients which characterized as the formation of secondary cancers at distant sites. Epithelial– mesenchymal transition (EMT) is a dynamic process that appear to facilitate tumor metastasis in various cancers by switching epithelial cells into mesenchymal properties. Although previous investigation suggested a key role of EMT transcriptional factors in suppression of E-cadherin, the association of these factors with other cellular regulators in cancer metastasis need to be fully elucidated. Post-translational modifications (PTMs), such as acetylation and phosphorylation, have emerged as an important mechanism to modulate biological behavior of substrate proteins. In this review, we summarized protein modification and subsequent function changes of Snail, Twist and ZEB, as well as their influence on tumor progression. Acetylation of EMT transcriptional factors usually cause nuclear localization and/or protein stabilization thus contribute to E-cadherin repression. Besides, Twist and ZEB were phosphorylated by diverse kinases to promote metastasis in many cancers, while Snail was negatively regulated by phosphorylation to degradation. Then, the potential of therapy for metastasis by targeting PTMs-involved regulation of EMT transcriptional factors were discussed.

scholarly journals Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial–mesenchymal transition by targetting PMEL through the Wnt signaling pathway

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Jiu-Jiang Wang ◽  
Zhi-Feng Li ◽  
Xiao-Jing Li ◽  
Zhao Han ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Melanoma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Melanoma Cells ◽  
Model Group ◽  
Mesenchymal Transition ◽  
E Cadherin

The study aims to evaluate the effects of miR-136 on the proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) of melanoma cells by targetting premelanosome protein (PMEL) through the Wnt signaling pathway. After establishment of melanoma mouse models, melanoma (model group) and normal tissues (normal group) were collected. Immunohistochemistry was performed to determine PMEL protein concentration. Mouse melanoma cells were assigned into control, blank, negative control (NC), miR-136 mimics, miR-136 inhibitors, siRNA-PMEL, and miR-136 inhibitors + siRNA-PMEL, LiC1 (Wnt signaling pathway activator), and siRNA-PMEL+ LiCl groups. MTT, Scratch test, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to evaluate miR-136, PMEL, β-catenin, Wnt3a, Bcl-2, Bax, Caspase, E-cadherin, and N-cadherin expressions. PMEL is highly expressed in melanoma tissues. MiR-136, Bax, Caspase, and E-cadherin expressions decreased in the model group, whereas PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions increased. Bax, Caspase, and E-cadherin expressions increased in the miR-136 mimics and siRNA-PMEL groups, whereas the expressions decreased in the miR-136 inhibitors group and LiC1 group. PMEL, β-catenin, Bcl-2, Wnt3a, and N-cadherin expressions, cell proliferation, migration, and invasion decreased, and the apoptosis rate inceased in the miR-136 mimics and siRNA-PMEL groups; whereas the tendencies were opposite to those in the miR-136 inhibitors group and LiC1 group. In the siRNA-PMEL+ LiCl group, PMEL expression decreased. These findings indicated that overexpression of miR-136 inhibits melanoma cell EMT, proliferation, migration, invasion, and promotes apoptosis by targetting PMEL through down-regulation of the Wnt signaling pathway.

Silencing of E-cadherin expression leads to increased chemosensitivity to irinotecan and oxaliplatin in colorectal cancer cell lines

2021 ◽  
pp. 096032712110214
Author(s):  
Veronika Skarkova ◽  
Adam Skarka ◽  
Monika Manethova ◽  
Afroditi A Stefanidi ◽  
Emil Rudolf
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Developed Countries ◽  
Convincing Evidence ◽  
Mesenchymal Transition ◽  
Real Time Analysis ◽  
Increased Sensitivity ◽  
Emt Markers ◽  
E Cadherin

Colorectal carcinoma (CRC) is a leading malignant disease in most developed countries. In advanced stages it presents with metastatic dissemination and significant chemoresistance. Despite intensive studies, no convincing evidence has been published concerning the association of cadherins and epithelial-mesenchymal transition (EMT) as a direct cause of acquired chemoresistance in CRC. The present study was designed to investigate the role of E-cadherin in EMT and its associated chemosensitivity/chemoresistance in four immortalized CRC cell lines representing various stages of CRC development (i.e. HT29 and Caco-2—early, SW480 and SW620 late). The expression of E-cadherin gene CDH1 was downregulated by the specific siRNA. Cell proliferation and chemosensitivity to irinotecan (IT) and oxaliplatin (OPT) were detected using WST-1 and x-CELLigence Real Time analysis. Expression of selected EMT markers were tested and compared using RT-PCR and western blot analysis in both variants (E-cadherin silenced and non-silenced) of each cell line. We have discovered that downregulation of E-cadherin expression has a diverse effect on both cell proliferation as well as the expression of EMT markers in individual tested CRC cell lines, with Caco-2 cells being the most responsive. On the other hand, reduced E-cadherin expression resulted in increased sensitivity of all cell lines to IT and mostly to OPT which might be related to changes in intracellular metabolism of these drugs. These results suggest dichotomy of E-cadherin involvement in the phenotypic EMT spectrum of CRC and warrants further mechanistic studies.

scholarly journals Expression and Clinical Utility of Transcription Factors Involved in Epithelial–Mesenchymal Transition during Thyroid Cancer Progression

2021 ◽  
Vol 10 (18) ◽  
pp. 4076
Author(s):  
Enke Baldini ◽  
Chiara Tuccilli ◽  
Daniele Pironi ◽  
Antonio Catania ◽  
Francesco Tartaglia ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Thyroid Cancer ◽  
Cancer Progression ◽  
Clinical Utility ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
E Cadherin

The transcription factors involved in epithelial–mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients’ clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

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