scholarly journals A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition

2011 ◽  
Vol 195 (3) ◽  
pp. 417-433 ◽  
Author(s):  
Nam Hee Kim ◽  
Hyun Sil Kim ◽  
Xiao-Yan Li ◽  
Inhan Lee ◽  
Hyung-Seok Choi ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Untranslated Regions ◽  
Loss Of Function ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Lung Carcinoma Cells ◽  
Cycle Regulation ◽  
Snail1 Expression

Snail1 is a zinc finger transcriptional repressor whose pathological expression has been linked to cancer cell epithelial–mesenchymal transition (EMT) programs and the induction of tissue-invasive activity, but pro-oncogenic events capable of regulating Snail1 activity remain largely uncharacterized. Herein, we demonstrate that p53 loss-of-function or mutation promotes cancer cell EMT by de-repressing Snail1 protein expression and activity. In the absence of wild-type p53 function, Snail1-dependent EMT is activated in colon, breast, and lung carcinoma cells as a consequence of a decrease in miRNA-34 levels, which suppress Snail1 activity by binding to highly conserved 3′ untranslated regions in Snail1 itself as well as those of key Snail1 regulatory molecules, including β-catenin, LEF1, and Axin2. Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression. These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs.

scholarly journals MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Zhenglei Xu ◽  
Zhichao Yu ◽  
Qinghong Tan ◽  
Cheng Wei ◽  
Qi Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Untranslated Regions ◽  
Cancer Cell Proliferation ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Novel Mirna ◽  
Gastric Cancer Cell Proliferation ◽  
And Migration

Abstract MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial–mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3′ untranslated regions (3′UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.

scholarly journals The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831770621 ◽  
Author(s):  
Hakan Kucuksayan ◽  
Hakan Akca
Keyword(s):  
Lung Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Binding Protein ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Carcinoma Cells ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition ◽  
Lung Carcinoma Cells

Epithelial–mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial–mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial–mesenchymal transition in cancer cells. However, crosstalks between p38 and Akt pathways involved in epithelial–mesenchymal transition are still unknown. We recently reported that there is a crosstalk between p38 and Akt pathways in non-small-cell lung carcinoma cells, and this crosstalk is associated with E-cadherin and special AT-rich sequence-binding protein 2 expressions. Therefore, we aimed to determine whether this crosstalk has a mediator role in the regulation of epithelial–mesenchymal transition in non-small-cell lung carcinoma. Our results showed that inhibition of p38 leads to the disruption of this crosstalk via decreased expression of phosphatase and tensin homolog (PTEN) and subsequently increased activation of Akt in non-small-cell lung carcinoma cells. Then, we found that p38 inhibition upregulated special AT-rich sequence-binding protein 2 expression and reversed epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. Furthermore, special AT-rich sequence-binding protein 2 knockdown abolished the effect of p38 inhibition on epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. In conclusion, our results strongly indicate that the crosstalk between p38 and Akt pathways can determine special AT-rich sequence-binding protein 2 expression and epithelial character of non-small-cell lung carcinoma cells, and special AT-rich sequence-binding protein 2 is a critical epigenetic regulator for epithelial–mesenchymal transition mediated by p38 pathway in non-small-cell lung carcinoma. Our findings will contribute to illuminate the molecular mechanisms of the epithelial–mesenchymal transition process that has a critical significance for lung cancer metastasis.

scholarly journals CircZNF652 accelerates the proliferation and migration of primary lung carcinoma cells by downregulating miR-766

2021 ◽  
Vol 20 (11) ◽  
pp. 2255-2260
Author(s):  
Xiaobing Hong ◽  
Yongqing Chen ◽  
Danzhen Zhang
Keyword(s):  
Lung Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Biological Functions ◽  
Mesenchymal Transition ◽  
Lung Carcinoma Cells ◽  
Kaplan Meier ◽  
Primary Lung Carcinoma ◽  
Knockdown Effect ◽  
And Migration

Purpose: To explore the biological functions and molecular mechanism of circZNF652 involvement in primary lung carcinoma.Methods: CircZNF652 levels in primary lung carcinoma cases and controls were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Its prognostic value in primary lung carcinoma was examined by depicting it with Kaplan-Meier curves. The biological functions of circZNF652 in regulating proliferative and migratory capacities in A549 and SPC-A-1 cells were analyzed from the curves. Interaction between circZNF652 and its downstream gene, miR-766, wasassessed, and their co-regulation on primary lung carcinoma was determined by rescue experiments.Results: CircZNF652 was abnormally and significantly upregulated in primary lung carcinoma cases (p< 0.05), resulting in a poor prognosis. The knockdown effect of circZNF652 attenuated the proliferative and migratory capacities of A549 and SPC-A-1 cells, and downregulated epithelial-mesenchymal transition (EMT)-associated genes. CircZNF652 bound and negatively regulated miR-766, a keydownstream gene involved in circZNF652-induced aggravation of primary lung carcinoma.Conclusion: CircZNF652 serves as an oncogene, triggering the aggravation of primary lung carcinoma by negatively regulating miR-766. The results of this study may provide new insights into the treatment of lung carcinoma.

INHIBITION OF MALIGNANT POTENTIAL AND EXPRESSION OF PROTEINS ASSOCIATED WITH EPITHELIAL-MESENCHYMAL TRANSITION IN LEWIS LUNG CARCINOMA CELLS TRANSDUCED WITH MURINE ifn-/3 GENE IN RECOMBINANT BACULOVIRUS

2016 ◽  
Vol 38 (1) ◽  
pp. 13-21
Author(s):  
O O Lykhova ◽  
O Kovalova ◽  
N Bezdenezhnykh ◽  
I Adamenko ◽  
A Vorontsova ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Recombinant Baculovirus ◽  
Malignant Potential ◽  
Carcinoma Cells ◽  
Lewis Lung ◽  
Mesenchymal Transition ◽  
Lung Carcinoma Cells ◽  
P Gene

Aim: To analyze biological characteristics, malignant potential and expression of protei.os associated with epithelial-mesenchymal transition in murine lung carcinoma cells transduced with interferon-beta (ifn-{J) gene in baculovirus vector. Materials and Meth­ ods; The study was performed on Lewis lung carcinoma (LL) ceUs transduced  with ifil-P gene in recombinant bacuJovirus vector. Biological characteristics of the LL cells were studied with the use of standard cell culture methods, cytogenetic and immunocyto­ chemical assays. Results: Recombinant baculovirus-mediated transduction ofLLcells with ifn-P gene resulted i.o significant decrease of cell growth rate and density both io compJete and serum-free medium.Also, LL ceUs transduction with ifn-P gene significantly inhibited ceU migration  in vitro.Transduction of LL cells by baculovirus vector with or without ifn-{J gene caused significant geno­ tox.ic effect  in these ceUs. Furthermore, ifn-{J gene transfer to lung carcinoma cells resulted in significant increase of nuclear ex­ pression ofpl(p       < 0.01), p21w.IJ'e (p < 0.001),cytoplasmlc expression ofE-cadherin (p < 0.005) and inhibition oftranscrlption factors of epithelial-mesenchymal transition (EMn Twist (p <0.005) and Slug (p < 0.00 I) expression.Condusions: Transduction with ij11-{J gene of LL cells in recombinant baculovirus resulted in acquirement of less malignant phenotype i11 vitro and suppressed expression of proteins associated with EMT.

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