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Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer

BACKGROUND: Our previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed t...

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Autores principales: Zhang, Jun, Lin, Zhongqiu, Gao, Yali, Yao, Tingting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216566/
https://www.ncbi.nlm.nih.gov/pubmed/28057015
http://dx.doi.org/10.1186/s13046-016-0472-2
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author Zhang, Jun
Lin, Zhongqiu
Gao, Yali
Yao, Tingting
author_facet Zhang, Jun
Lin, Zhongqiu
Gao, Yali
Yao, Tingting
author_sort Zhang, Jun
collection PubMed
description BACKGROUND: Our previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed to further elucidate the role and potential inactivation mechanism of MEG3 in cervical cancer. METHODS: ROC curve and Cox regression analyses were used to assess the diagnostic and prognostic value of MEG3 in patients with cervical cancer. The methylation status of the MEG3 promoter in cervical cancer tissue samples was tested using methylation-specific PCR. Furthermore, we altered the methylation status of the MEG3 promoter in two cervical cancer cell lines (HeLa and CaSki) using a DNA methylation transfer enzyme inhibitor (5-Aza-CdR), to investigate whether promoter hypermethylation is a potential cause of MEG3 inactivation. Finally, we used CCK-8 and colony formation assays to evaluate the cell proliferation ability of HeLa and CaSki cells that had been treated with 5-aza-CdR, to investigate whether downregulation of MEG3 caused by promoter hypermethylation had biological effects. RESULTS: ROC curve analysis indicated that MEG3 status showed sufficient sensitivity and specificity for prediction of tumor size and lymph node metastasis in patients with cervical cancer. In addition, our follow-up data showed that low MEG3 expression was correlated with recurrence and short overall survival. Moreover, hypermethylation of the MEG3 promoter was observed in most cervical cancer tissue samples, and demethylation of the MEG3 promoter led to re-expression of MEG3 and inhibited proliferation of HeLa and CaSki cells. CONCLUSIONS: MEG3 is a powerful tool for diagnosis and prognosis of patients with cervical cancer, and low expression of MEG3 is likely to be related to promoter hypermethylation in cervical cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0472-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-52165662017-01-09 Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer Zhang, Jun Lin, Zhongqiu Gao, Yali Yao, Tingting J Exp Clin Cancer Res Research BACKGROUND: Our previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed to further elucidate the role and potential inactivation mechanism of MEG3 in cervical cancer. METHODS: ROC curve and Cox regression analyses were used to assess the diagnostic and prognostic value of MEG3 in patients with cervical cancer. The methylation status of the MEG3 promoter in cervical cancer tissue samples was tested using methylation-specific PCR. Furthermore, we altered the methylation status of the MEG3 promoter in two cervical cancer cell lines (HeLa and CaSki) using a DNA methylation transfer enzyme inhibitor (5-Aza-CdR), to investigate whether promoter hypermethylation is a potential cause of MEG3 inactivation. Finally, we used CCK-8 and colony formation assays to evaluate the cell proliferation ability of HeLa and CaSki cells that had been treated with 5-aza-CdR, to investigate whether downregulation of MEG3 caused by promoter hypermethylation had biological effects. RESULTS: ROC curve analysis indicated that MEG3 status showed sufficient sensitivity and specificity for prediction of tumor size and lymph node metastasis in patients with cervical cancer. In addition, our follow-up data showed that low MEG3 expression was correlated with recurrence and short overall survival. Moreover, hypermethylation of the MEG3 promoter was observed in most cervical cancer tissue samples, and demethylation of the MEG3 promoter led to re-expression of MEG3 and inhibited proliferation of HeLa and CaSki cells. CONCLUSIONS: MEG3 is a powerful tool for diagnosis and prognosis of patients with cervical cancer, and low expression of MEG3 is likely to be related to promoter hypermethylation in cervical cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0472-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-05 /pmc/articles/PMC5216566/ /pubmed/28057015 http://dx.doi.org/10.1186/s13046-016-0472-2 Text en © The Author(s). 2017 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
Zhang, Jun
Lin, Zhongqiu
Gao, Yali
Yao, Tingting
Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title_full Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title_fullStr Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title_full_unstemmed Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title_short Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
title_sort downregulation of long noncoding rna meg3 is associated with poor prognosis and promoter hypermethylation in cervical cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216566/
https://www.ncbi.nlm.nih.gov/pubmed/28057015
http://dx.doi.org/10.1186/s13046-016-0472-2
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