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YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability

Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was...

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Autores principales: Wei, Xudong, Liu, Fenglei, Jiang, Xuelian, Xu, Xiaoyan, Zhou, Tianhao, Kang, Chengfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421032/
https://www.ncbi.nlm.nih.gov/pubmed/34497757
http://dx.doi.org/10.3389/fonc.2021.692405
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author Wei, Xudong
Liu, Fenglei
Jiang, Xuelian
Xu, Xiaoyan
Zhou, Tianhao
Kang, Chengfang
author_facet Wei, Xudong
Liu, Fenglei
Jiang, Xuelian
Xu, Xiaoyan
Zhou, Tianhao
Kang, Chengfang
author_sort Wei, Xudong
collection PubMed
description Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was detected by RT-qPCR and Western blot analysis. An interaction of YY1, GAS5, and p53 protein stability was predicted and confirmed by bioinformatics, ChIP, Co-IP, RIP, and FISH assays. Following loss- and gain-function assays, LSCC cell proliferation, colony formation, cell cycle, telomere length and telomerase activity were evaluated by CCK-8 assay, colony formation assay, flow cytometry, and PCR-ELISA, respectively. Nude mice were xenografted with the tumor in vivo. LSCC cell lines presented with upregulated expression of YY1, downregulated GAS5 expression, and decreased p53 stability. YY1 inhibited the expression of GAS5, which in turn recruited p300 and bound to p53, thus stabilizing it. Moreover, YY1 could directly interact with p300 and suppressp53 stability, leading to enhancement of cell proliferation, telomere length and telomerase activity in vitro along with tumor growth in vivo. Collectively, YY1 can stimulate proliferation and telomerase activity of LSCC cells through suppression of GAS5-dependent p53 stabilization or by decreasing p53 stability via a direct interaction with p300, suggesting that YY1 presents a therapeutic target as a potential oncogene in LSCC development and progression.
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spelling pubmed-84210322021-09-07 YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability Wei, Xudong Liu, Fenglei Jiang, Xuelian Xu, Xiaoyan Zhou, Tianhao Kang, Chengfang Front Oncol Oncology Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was detected by RT-qPCR and Western blot analysis. An interaction of YY1, GAS5, and p53 protein stability was predicted and confirmed by bioinformatics, ChIP, Co-IP, RIP, and FISH assays. Following loss- and gain-function assays, LSCC cell proliferation, colony formation, cell cycle, telomere length and telomerase activity were evaluated by CCK-8 assay, colony formation assay, flow cytometry, and PCR-ELISA, respectively. Nude mice were xenografted with the tumor in vivo. LSCC cell lines presented with upregulated expression of YY1, downregulated GAS5 expression, and decreased p53 stability. YY1 inhibited the expression of GAS5, which in turn recruited p300 and bound to p53, thus stabilizing it. Moreover, YY1 could directly interact with p300 and suppressp53 stability, leading to enhancement of cell proliferation, telomere length and telomerase activity in vitro along with tumor growth in vivo. Collectively, YY1 can stimulate proliferation and telomerase activity of LSCC cells through suppression of GAS5-dependent p53 stabilization or by decreasing p53 stability via a direct interaction with p300, suggesting that YY1 presents a therapeutic target as a potential oncogene in LSCC development and progression. Frontiers Media S.A. 2021-08-23 /pmc/articles/PMC8421032/ /pubmed/34497757 http://dx.doi.org/10.3389/fonc.2021.692405 Text en Copyright © 2021 Wei, Liu, Jiang, Xu, Zhou and Kang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wei, Xudong
Liu, Fenglei
Jiang, Xuelian
Xu, Xiaoyan
Zhou, Tianhao
Kang, Chengfang
YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title_full YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title_fullStr YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title_full_unstemmed YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title_short YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
title_sort yy1 promotes telomerase activity and laryngeal squamous cell carcinoma progression through impairment of gas5-mediated p53 stability
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421032/
https://www.ncbi.nlm.nih.gov/pubmed/34497757
http://dx.doi.org/10.3389/fonc.2021.692405
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