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Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance

The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. I...

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Autores principales: Tang, Huaping, Chen, Jianyou, Han, Xiaolei, Feng, Yan, Wang, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116663/
https://www.ncbi.nlm.nih.gov/pubmed/33996808
http://dx.doi.org/10.3389/fcell.2021.646390
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author Tang, Huaping
Chen, Jianyou
Han, Xiaolei
Feng, Yan
Wang, Fang
author_facet Tang, Huaping
Chen, Jianyou
Han, Xiaolei
Feng, Yan
Wang, Fang
author_sort Tang, Huaping
collection PubMed
description The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 (SPP1) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of SPP1 in tumor tissues was significantly higher than normal tissues. The high expression of SPP1 was also correlated with tumor grade and poor clinical prognosis. To understand the roles of SPP1 and the DNA methyltransferase 1 (DNMT1), which regulated SPP1 expression, in affecting cell viability, migration and invasion, SPP1 and DNMT1 were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that SPP1 promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down SPP1 in cells restored sensitivity to cisplatin. Further, A549 cells without SPP1 overexpression demonstrated lower tumor growth rate than SPP1 overexpression cells using the xenograft tumor mouse model. High expression of SPP1 in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by DNMT1. Our data suggested that SPP1 can be used as a marker for highly malignant lung cancer and targeting SPP1 may be a potential lung cancer treatment strategy.
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spelling pubmed-81166632021-05-14 Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance Tang, Huaping Chen, Jianyou Han, Xiaolei Feng, Yan Wang, Fang Front Cell Dev Biol Cell and Developmental Biology The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 (SPP1) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of SPP1 in tumor tissues was significantly higher than normal tissues. The high expression of SPP1 was also correlated with tumor grade and poor clinical prognosis. To understand the roles of SPP1 and the DNA methyltransferase 1 (DNMT1), which regulated SPP1 expression, in affecting cell viability, migration and invasion, SPP1 and DNMT1 were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that SPP1 promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down SPP1 in cells restored sensitivity to cisplatin. Further, A549 cells without SPP1 overexpression demonstrated lower tumor growth rate than SPP1 overexpression cells using the xenograft tumor mouse model. High expression of SPP1 in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by DNMT1. Our data suggested that SPP1 can be used as a marker for highly malignant lung cancer and targeting SPP1 may be a potential lung cancer treatment strategy. Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC8116663/ /pubmed/33996808 http://dx.doi.org/10.3389/fcell.2021.646390 Text en Copyright © 2021 Tang, Chen, Han, Feng and Wang. 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 Cell and Developmental Biology
Tang, Huaping
Chen, Jianyou
Han, Xiaolei
Feng, Yan
Wang, Fang
Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title_full Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title_fullStr Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title_full_unstemmed Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title_short Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
title_sort upregulation of spp1 is a marker for poor lung cancer prognosis and contributes to cancer progression and cisplatin resistance
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116663/
https://www.ncbi.nlm.nih.gov/pubmed/33996808
http://dx.doi.org/10.3389/fcell.2021.646390
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