scholarly journals EZH2 and KDM6B Expressions Are Associated with Specific Epigenetic Signatures during EMT in Non Small Cell Lung Carcinomas

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3649
Author(s):  
Camille Lachat ◽  
Diane Bruyère ◽  
Amandine Etcheverry ◽  
Marc Aubry ◽  
Jean Mosser ◽  
...  

The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the histone demethylase KDM6B (Lysine Demethylase 6B), which can remove the H3K27me3 mark. Nevertheless, it still remains unclear how these enzymes, with apparent opposite activities, could both promote EMT. In this study, we evaluated the function of these two enzymes using an EMT-inducible model, the lung cancer A549 cell line. ChIP-seq coupled with transcriptomic analysis showed that EZH2 and KDM6B were able to target and modulate the expression of different genes during EMT. Based on this analysis, we described INHBB, WTN5B, and ADAMTS6 as new EMT markers regulated by epigenetic modifications and directly implicated in EMT induction.

2021 ◽  
pp. FSO747
Author(s):  
Neeti Sharma ◽  
Piyush W Raut ◽  
Meghna M Baruah ◽  
Akshay Sharma

Aim: We have previously reported that quercetin (Qu) regulates epithelial–mesenchymal transition (EMT) by modulating Wnt signaling components. In this study, we investigated the synergistic effect of Qu and 2-methoxyestradiol (2-ME) and the role of Wnt signaling components in regulating EMT in PC-3 cells. Materials & methods: EMT was induced by treating PC-3 cells with TGF-β, followed by evaluation of expression of EMT markers and Wnt signaling proteins in naive, induced and after exposing induced cells to Qu and 2-ME at both gene and protein level by real-time PCR (RT-PCR) and western blot, respectively. Results: Qu and 2-ME synergistically downregulated mesenchymal markers with simultaneous upregulation of epithelial markers. Wnt signaling proteins expression was also downregulated by Qu and 2-ME in TGF-β-induced EMT in PC-3 cells. Conclusion: Thus, combination therapy of Qu and 2-ME could be a new promising therapeutic approach for the treatment of prostate cancer.


2021 ◽  
Vol 10 (4) ◽  
pp. 1804-1818
Author(s):  
Jara Martín ◽  
Joan Josep Castellano ◽  
Ramón María Marrades ◽  
Jordi Canals ◽  
Nuria Viñolas ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22021-e22021
Author(s):  
Angelica Figueroa ◽  
Vanessa Abella ◽  
Guadalupe Aparicio ◽  
Mar Haz-Conde ◽  
Javier Gayo ◽  
...  

e22021 Background: Given the role of vinflunine (VFL) in the microtubule dynamics and the link between microtubules and cell adhesions through cadherins, we have investigated the possible influence of VFL on adherens junctions through its interaction with microtubules. We have studied the implication of VFL on the reversion of epithelial-mesenchymal transition (EMT) in bladder transitional cell carcinoma and explored a possible novel molecular mechanism. Methods: Four human bladder transitional carcinoma cell lines were used to carry out the following experimental procedure: Cytotoxicity assay by using MTT assay, qRTPCR to analyze mRNA markers of the EMT, Western blotting using specific antibodies for EMT markers, and immunofluorescence images, analyzed by epifluorescence microscopy. Results: Cell growth reduction was detected in human bladder carcinoma cells under VFL treatment compared to control. VFL induces mesenchymal to epithelial phenotype and modulates the EMT markers: E-cadherin and Cytokeratin-19 were enhanced under treatment, while significantly reduction of mRNA mesenchymal markers expression (Vimentin, N-cadherin) and EMT-transcriptional factors (Snail and Zeb1) was detected. Strong reduction of Hakai protein was seen under VFL treatment. Hakai was discovered as an E3 ubiquitin-ligase that mediates the posttranslational downregulation of E-cadherin. Epifluorescence images showed that VFL treatment promotes E-cadherin localization specifically at cell-cell contact; while, Hakai expression decreases its expression in the nuclei and cytoplasm. Conclusions: These results suggest that VFL up-regulates E-cadherin contributing to mesenchymal to epithelial transition, and that Hakai modulation might be the molecular mechanism by which the increasing E-cadherin at cell-cell contacts in bladder carcinoma cell lines is detected. Given the relevant in vitro role of VFL on E-cadherin expression and on the reversion of EMT process, we hypothesized that VFL could exert a clinical benefit in delaying the metastasis in urothelial tumors.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1178 ◽  
Author(s):  
Jun-Ting Cheng ◽  
Lingzhi Wang ◽  
Hong Wang ◽  
Feng-Ru Tang ◽  
Wen-Qi Cai ◽  
...  

Long non-coding RNAs (lncRNAs) are versatile regulators of gene expression and play crucial roles in diverse biological processes. Epithelial-mesenchymal transition (EMT) is a cellular program that drives plasticity during embryogenesis, wound healing, and malignant progression. Increasing evidence shows that lncRNAs orchestrate multiple cellular processes by modulating EMT in diverse cell types. Dysregulated lncRNAs that can impact epithelial plasticity by affecting different EMT markers and target genes have been identified. However, our understanding of the landscape of lncRNAs important in EMT is far from complete. Here, we summarize recent findings on the mechanisms and roles of lncRNAs in EMT and elaborate on how lncRNAs can modulate EMT by interacting with RNA, DNA, or proteins in epigenetic, transcriptional, and post-transcriptional regulation. This review also highlights significant EMT pathways that may be altered by diverse lncRNAs, thereby suggesting their therapeutic potential.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 806 ◽  
Author(s):  
Yariswamy Manjunath ◽  
Sathisha V. Upparahalli ◽  
Diego M. Avella ◽  
Chelsea B. Deroche ◽  
Eric T. Kimchi ◽  
...  

In addition to the FDA-approved definition of a circulating tumor cell (CTC), various CTC phenotypes have been discovered. Epithelial-mesenchymal transition (EMT) of cancer cells is directly linked to PD-L1 upregulation. The goal of the study was to investigate PD-L1 expression and EMT in CTCs of non-small cell lung cancer (NSCLC) patients, and perform an outcome analysis. Prospectively, 7.5 mL peripheral blood was collected from 30 NSCLC patients that underwent surgery and 15 healthy controls. CTCs were enriched by size-based microfilter and immunofluorescence stainings performed (cytokeratin (CK) 8/18/19, EpCAM, CD45, PD-L1, EMT markers vimentin, and N-Cadherin, DAPI). Patient-matched NSCLC tissues were also stained. CTC staining intensity was quantified with a software and correlated with patient-matched NSCLC tissues and survival. PD-L1 and EMT markers were expressed at significantly higher proportions in CTCs than patient-matched NSCLC tissues (p < 0.05); ≥3 PD-L1pos/EMTposCTCs were associated with significantly poorer survival after curative surgery (p < 0.05). No CTCs were detected in 15 healthy controls. This study shows that PD-L1 expression and EMT of CTCs is a negative survival predictor for NSCLC patients. The therapeutic role of the molecular linkage of PD-L1 and EMT will need to be further investigated, as linked pathways could be targeted to improve NSCLC outcome.


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