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Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition

BACKGROUND: Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was fur...

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Autores principales: Liu, Xian, Feng, Qian, Zhang, Yanru, Zheng, PengSheng, Cui, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944906/
https://www.ncbi.nlm.nih.gov/pubmed/33691694
http://dx.doi.org/10.1186/s12935-021-01858-3
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author Liu, Xian
Feng, Qian
Zhang, Yanru
Zheng, PengSheng
Cui, Nan
author_facet Liu, Xian
Feng, Qian
Zhang, Yanru
Zheng, PengSheng
Cui, Nan
author_sort Liu, Xian
collection PubMed
description BACKGROUND: Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study. METHODS: RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation. RESULTS: Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. CONCLUSIONS: These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01858-3.
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spelling pubmed-79449062021-03-10 Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition Liu, Xian Feng, Qian Zhang, Yanru Zheng, PengSheng Cui, Nan Cancer Cell Int Primary Research BACKGROUND: Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study. METHODS: RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation. RESULTS: Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. CONCLUSIONS: These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01858-3. BioMed Central 2021-03-10 /pmc/articles/PMC7944906/ /pubmed/33691694 http://dx.doi.org/10.1186/s12935-021-01858-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Liu, Xian
Feng, Qian
Zhang, Yanru
Zheng, PengSheng
Cui, Nan
Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title_full Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title_fullStr Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title_full_unstemmed Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title_short Absence of EpCAM in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
title_sort absence of epcam in cervical cancer cells is involved in sluginduced epithelial‐mesenchymal transition
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944906/
https://www.ncbi.nlm.nih.gov/pubmed/33691694
http://dx.doi.org/10.1186/s12935-021-01858-3
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