scholarly journals Epithelial–Mesenchymal Transition Participates in the Formation of Vestibular Flat Epithelium

2021 ◽  
Vol 14 ◽  
Author(s):  
Lu He ◽  
Guo-Peng Wang ◽  
Jing-Ying Guo ◽  
Zhong-Rui Chen ◽  
Ke Liu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Adhesion ◽  
Microarray Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Mesenchymal Transition ◽  
Cell Markers ◽  
Qrt Pcr

The vestibular sensory epithelium of humans and mice may degenerate into a layer of flat cells, known as flat epithelium (FE), after a severe lesion. However, the pathogenesis of vestibular FE remains unclear. To determine whether the epithelial–mesenchymal transition (EMT) participates in the formation of vestibular FE, we used a well-established mouse model in which FE was induced in the utricle by an injection of streptomycin into the inner ear. The mesenchymal and epithelial cell markers and cell proliferation were examined using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The function of the EMT was assessed through transcriptome microarray analysis. The results demonstrated that mesenchymal cell markers (α-SMA, S100A4, vimentin, and Fn1) were upregulated in vestibular FE compared with the normal utricle. Robust cell proliferation, which was absent in the normal status, was observed in the formation of FE. Microarray analysis identified 1,227 upregulated and 962 downregulated genes in vestibular FE. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were highly associated with several EMT-related GO terms, such as cell adhesion, cell migration, and extracellular matrix. Pathway enrichment analysis revealed that DEGs were enriched in the EMT-related signaling pathways, including extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/Akt signaling pathway and cell adhesion molecule. Protein–protein interaction networks screened 20 hub genes, which were Akt, Casp3, Col1a1, Col1a2, Fn1, Hgf, Igf1,Il1b, Irs1, Itga2, Itga5, Jun, Mapk1, Myc, Nras, Pdgfrb, Tgfb1, Thbs1, Trp53, and Col2a1. Most of these genes are reportedly involved in the EMT process in various tissues. The mRNA expression level of hub genes was validated using qRT-PCR. In conclusion, the present study indicates that EMT plays a significant role in the formation of vestibular FE and provides an overview of transcriptome characteristics in vestibular FE.

Long noncoding RNA XIST regulates the EGF receptor to promote TGF-β1-induced epithelial–mesenchymal transition in pancreatic cancer

2020 ◽  
Vol 98 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Lei Zou ◽  
Feng-Rong Chen ◽  
Ren-Pin Xia ◽  
Hua-Wei Wang ◽  
Zhen-Rong Xie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Clinical Specimens ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Tgf Β1

Background: This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial–mesenchymal transition (EMT) in pancreatic cancer (PC). Methods: Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST. Results: Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-β1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a. Conclusions: XIST promotes TGF-β1-induced EMT by regulating the miR-34a–YAP–EGFR axis in PC.

miR-653 Induces Bone Marrow Mesenchymal Stem Cells Proliferation via Activating Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

2022 ◽  
Vol 12 (2) ◽  
pp. 381-385
Author(s):  
Cui Qin ◽  
Yibo Xiang ◽  
Sheng Li ◽  
Shu Huang ◽  
Wenjun Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Transcription Factor ◽  
Epithelial Mesenchymal Transition ◽  
Biological Mechanism ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Marrow Mesenchymal Stem Cells

This study intends to assess miR-653’s expression in MSCs and OSCC and discuss molecular biological mechanism of changes of EMT in MSCs through activating miR-653 in OSCC. miR-653 expression in MSCs and OSCC was detected. si-miR-653 was transfected into MSCs followed by analysis of cell proliferation by CCK-8 and clone formation assay, cell apoptosis and cycle by FCM, and the changes of transcription factor as ZEB1 and Snail by qRT-PCR. miR-653 expression in OSCC cell was up-regulated significantly from the result of q-RT-PCR detection. The proliferation of MSCs induced by miR-653 was restrained and apoptotic rate was increased after treatment with si-miR-653 along with stagnated cycle of G1/G0 staging cell. The expression of transcription factor of EMT type as ZEB1 and Snail was elevated significantly after intervention using si-miR-653. In conclusion, the proliferation of OSCC could be induced by MSCs through activation with miR-653 which might be through regulation of EMT process.

scholarly journals Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion

2020 ◽  
Author(s):  
Sina Ibne Noor ◽  
Marcus Hoffmann ◽  
Natalie Rinis ◽  
Markus F. Bartels ◽  
Patrick Winterhalter ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Adhesion Properties ◽  
Knock Out ◽  
Mesenchymal Transition ◽  
Transcriptional Changes ◽  
Cell Cell

AbstractDefects in protein O-mannosylation lead to severe congenital muscular dystrophies known as α-dystroglycanopathy. A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which leads to a reduction in cell adhesion to the extracellular matrix. Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, are mainly associated with muscle-eye-brain (MEB) disease. In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1. However, direct molecular mechanisms are largely unknown. We used POMGNT1 knock-out HEK293T cells and fibroblasts from a MEB patient to gain a deeper insight into the molecular changes in POMGNT1 deficiency. A combination of biochemical and molecular biological techniques with proteomics, glycoproteomics and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion. We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh). In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions. We found that in POMGNT1 deficient cells ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable to the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype. Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general, and suggests a previously underestimated impact of changes in O-mannosylation on N-glycosylation.

scholarly journals PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangjin Chen ◽  
Jiwei Sun ◽  
Mengru Xie ◽  
Shaoling Yu ◽  
Qingming Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Neck Squamous Cell Carcinoma ◽  
Pathway Enrichment Analysis ◽  
Mesenchymal Transition

Plasminogen activator, urokinase (uPA) is a secreted serine protease whose Dysregulation is often accompanied by various cancers. However, the biological functions and potential mechanisms of PLAU in head and neck squamous cell carcinoma (HNSCC) remain undetermined. Here, the expression, prognosis, function, and coexpression genetic networks of PLAU in HNSCC were investigated by a series of public bioinformatics tools. A Higher PLAU level predicted a poorer clinical outcome. Meanwhile, functional network analysis implied that PLAU and associated genes mainly regulated cell-substrate adhesion, tissue migration, and extracellular matrix binding. The top 4 significantly associated genes are C10orf55, ITGA5, SERPINE1, and TNFRSF12A. Pathway enrichment analysis indicated that PLAU might activate the epithelial-to-mesenchymal transition (EMT) process, which could explain the poor prognosis in HNSCC. Besides, genes associated with PLAU were also enriched in EMT pathways. We further validated the bioinformatics analysis results by in vivo and in vitro experiments. Then, we found that much more PLAU was detected in HNSCC tissues, and the silencing of PLAU inhibit the proliferation, migration, and EMT process of CAL27 cell lines. Notably, the downregulation of PLAU decreased the expression of TNFRSF12A. Moreover, knockdown TNFRSF12A also inhibits cell proliferation and migration. In vivo experiment results indicated that PLAU inhibition could suppress tumor growth. Collectively, PLAU is necessary for tumor progression and can be a diagnostic and prognostic biomarker in HNSCC.

scholarly journals Polygonum Barbatum Extract Reduces Colorectal Cancer Cell Proliferation, Migration, Invasion, and Epithelial-mesenchymal Transition via Regulation of the YAP and β-catenin Pathways

2021 ◽  
Author(s):  
Pi-Kai Chang ◽  
I-Chuan Yen ◽  
Wei-Cheng Tsai ◽  
Shih-Yu Lee
Keyword(s):  
Extracellular Matrix ◽  
Cell Growth ◽  
Cancer Cell ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pathway Enrichment Analysis ◽  
Human Colon Cancer ◽  
Mesenchymal Transition

Abstract BackgroundColorectal cancer (CRC) is the third most common cancer worldwide, but the development of novel therapeutics for CRC remains a challenge. Polygonum barbatum has anticancer potential, but its mechanism of action requires further investigation. This study was designed to investigate the inhibitory effect of Polygonum barbatum on human CRC cells. The HPLC fingerprints of the Polygonum barbatum extract (PBE) and quercetin standard were determined using analytical RP-HPLC and evaluations were completed using the human colon cancer cell line HCT-116 (KRASG13D mutation) and HT-29 cells. After treatment with PBE, cell viability, colony formation, migration, invasion, and apoptosis were analyzed using CCK-8, colony formation, wound healing, Transwell invasion, and flow cytometry assays, respectively. RNA-sequencing, western blotting, and co-immunoprecipitation were also used to analyze changes in the whole-transcriptome of these cells and identify possible mechanisms of action for PBE in CRC cells. ResultsPBE significantly reduced CRC cell growth, migration, and invasion, and Gene Ontology analysis showed that the genes responsible for extracellular matrix organization, cell motility, and cell growth were suppressed by PBE. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the differentially expressed genes revealed that PBE treatment exerted a significant effect on the extracellular matrix interaction and focal adhesion pathways. Consistently, epithelial-to-mesenchymal transition markers, including N-cadherin, vimentin, SLUG, and SNAIL, were also all shown to be regulated by PBE. These effects were associated with blockade of the Yes-associated protein and the GSK3β/β-catenin axis.ConclusionPolygonum barbatum extract exerts a significant inhibitory effect on CRC cells and may be potentially applicable in clinical trials.

scholarly journals Kaiso (ZBTB33) Downregulation by Mirna-181a Inhibits Cell Proliferation, Invasion, and the Epithelial–Mesenchymal Transition in Glioma Cells

2018 ◽  
Vol 48 (3) ◽  
pp. 947-958 ◽  
Author(s):  
Ligang Wang ◽  
Jichao Ma ◽  
Xiaoxiong Wang ◽  
Fei Peng ◽  
Xin Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Opposite Effect ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Inhibitory Effects ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Qrt Pcr

Background/Aims: Kaiso (ZBTB33) expression is closely associated with the progression of many cancers and microRNA (miRNA) processing. MiR-181a plays critical roles in multiple cancers; however, its precise mechanisms in glioma have not been well clarified. The goal of this study was to evaluate the interaction between Kaiso and miR-181a in glioma. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the levels of Kaiso and miR-181a in glioma tissues and cell lines. Cell proliferation, invasion, and the epithelial–mesenchymal transition (EMT) were evaluated to analyze the biological functions of miR-181a and Kaiso in glioma cells. The mRNA and protein levels of Kaiso were measured by qRT-PCR and western blotting, respectively. Meanwhile, luciferase assays were performed to validate Kaiso as a miR-181a target in glioma cells. Results: We found that the level of miR-181a was the lowest among miR-181a–d in glioma tissues and cell lines, and the low level of miR-181a was closely associated with the increased expression of Kaiso in glioma tissues. Moreover, transfection of miR-181a significantly inhibited the proliferation, invasion, and EMT of glioma cells, whereas knockdown of miR-181a had the opposite effect. Bioinformatics analysis predicted that Kaiso was a potential target gene of miR-181a, and the luciferase reporter assay demonstrated that miR-181a could directly target Kaiso. In addition, Kaiso silencing had similar effects as miR-181a overexpression in glioma cells, whereas overexpression of Kaiso in glioma cells partially reversed the inhibitory effects of the miR-181a mimic. Conclusionss: miR-181a inhibited the proliferation, invasion, and EMT of glioma cells by directly targeting and downregulating Kaiso expression.

RNF185-AS1 Promotes Hepatocellular Carcinoma Progression Through Targeting miR-221-5p/integrin β5 Axis

2020 ◽  
Author(s):  
Chunmei Huang ◽  
Ke Li ◽  
Rongfu Huang ◽  
Jianhua Zhu ◽  
Jiayao Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
And Migration

Abstract Background: Recently, long noncoding RNAs (lncRNAs) have been reported to play important role in pathogenesis of various cancers. However, the function of RNF185-AS1 in hepatocellular carcinoma (HCC) metastasis has not been well investigated. The present study aims to explore the role and mechanism of RNF185-AS1 in hepatocellular carcinoma metastasis. Methods: The RNF185-AS1 expression in HCC cells and tissues was measured by quantitative real‐time polymerase chain reaction (qRT-PCR). The functional effects of RNF185-AS1 on tumor cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were assessed by Cell Counting Kit-8 (CCK8) assay, colony formation assay, transwell assay and Western blot. The luciferase reporters assay, RNA-binding protein immunoprecipitation assay, qRT-PCR and Western blot were performed to explore and confirm the interaction between RNF185-AS1 and miR-221-5p and integrin β5. The role of RNF185-AS1 in tumor progression was explored through in vivo experiments.Results: RNF185-AS1 was highly expressed in HCC tissues and cell lines. High levels of RNF185-AS1 was correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. RNF185-AS1 knockdown inhibited cell proliferation, migration, invasion and EMT. Additionally, RNF185-AS1 acted as a sponge for miR-221-5p and integrin β5 was identified as a target gene of miR-221-5p. Rescue assays showed that miR-221-5p inhibitor or integrin β5 overexpression rescued the function of RNF185-AS1 knockdown on cell proliferation, migration, invasion and EMT. Moreover, we found that RNF185-AS1 knockdown inhibited tumor metastases in xenograft tumor mouse model. Conclusion: Our findings demonstrated that RNF185-AS1 promoted cell EMT and migration by regulating miR-221-5p/integrin β5 axis in HCC.

scholarly journals Modulating Tumor Cell Functions by Tunable Nanopatterned Ligand Presentation

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Model Systems ◽  
Cellular Functions ◽  
Biophysical Parameters ◽  
Ligand Density ◽  
Mesenchymal Transition ◽  
Cell Functions

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

Sign in / Sign up

Export Citation Format

Share Document