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Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer
BACKGROUND: This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer. METHODS: Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 pa...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245611/ https://www.ncbi.nlm.nih.gov/pubmed/30453909 http://dx.doi.org/10.1186/s12885-018-5033-y |
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author | Wang, Longsheng Chen, Shaojun Zhang, Ziwei Zhang, Junfeng Mao, Shiyu Zheng, Jiayi Xuan, Yang Liu, Mengnan Cai, Keke Zhang, Wentao Guo, Yadong Zhai, Wei Yao, Xudong |
author_facet | Wang, Longsheng Chen, Shaojun Zhang, Ziwei Zhang, Junfeng Mao, Shiyu Zheng, Jiayi Xuan, Yang Liu, Mengnan Cai, Keke Zhang, Wentao Guo, Yadong Zhai, Wei Yao, Xudong |
author_sort | Wang, Longsheng |
collection | PubMed |
description | BACKGROUND: This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer. METHODS: Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP–LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown. RESULTS: The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum. CONCLUSIONS: The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer. |
format | Online Article Text |
id | pubmed-6245611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62456112018-11-26 Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer Wang, Longsheng Chen, Shaojun Zhang, Ziwei Zhang, Junfeng Mao, Shiyu Zheng, Jiayi Xuan, Yang Liu, Mengnan Cai, Keke Zhang, Wentao Guo, Yadong Zhai, Wei Yao, Xudong BMC Cancer Research Article BACKGROUND: This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer. METHODS: Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP–LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown. RESULTS: The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum. CONCLUSIONS: The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer. BioMed Central 2018-11-20 /pmc/articles/PMC6245611/ /pubmed/30453909 http://dx.doi.org/10.1186/s12885-018-5033-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Article Wang, Longsheng Chen, Shaojun Zhang, Ziwei Zhang, Junfeng Mao, Shiyu Zheng, Jiayi Xuan, Yang Liu, Mengnan Cai, Keke Zhang, Wentao Guo, Yadong Zhai, Wei Yao, Xudong Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title | Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title_full | Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title_fullStr | Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title_full_unstemmed | Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title_short | Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
title_sort | suppressed ogt expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245611/ https://www.ncbi.nlm.nih.gov/pubmed/30453909 http://dx.doi.org/10.1186/s12885-018-5033-y |
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