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hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer
PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485037/ https://www.ncbi.nlm.nih.gov/pubmed/31114249 http://dx.doi.org/10.2147/OTT.S192568 |
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author | Li, Nan Tian, Guang-Wei Tang, Ling-Rong Li, Guang |
author_facet | Li, Nan Tian, Guang-Wei Tang, Ling-Rong Li, Guang |
author_sort | Li, Nan |
collection | PubMed |
description | PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT. |
format | Online Article Text |
id | pubmed-6485037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64850372019-05-21 hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer Li, Nan Tian, Guang-Wei Tang, Ling-Rong Li, Guang Onco Targets Ther Original Research PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT. Dove Medical Press 2019-04-23 /pmc/articles/PMC6485037/ /pubmed/31114249 http://dx.doi.org/10.2147/OTT.S192568 Text en © 2019 Li et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Li, Nan Tian, Guang-Wei Tang, Ling-Rong Li, Guang hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title | hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title_full | hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title_fullStr | hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title_full_unstemmed | hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title_short | hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
title_sort | hmof reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485037/ https://www.ncbi.nlm.nih.gov/pubmed/31114249 http://dx.doi.org/10.2147/OTT.S192568 |
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