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The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy
Breast cancer (BC) is the most common tumor in women, and the molecular mechanism underlying its pathogenesis remains unclear. In this study, we aimed to investigate gene modules related to the phenotypes of BC, and identify representative candidate biomarkers for clinical prognosis of BC patients....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787223/ https://www.ncbi.nlm.nih.gov/pubmed/35087836 http://dx.doi.org/10.3389/fcell.2021.798221 |
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author | Liu, Jiazhou Wang, Xiaoyu Sun, Jiazheng Chen, Yuru Li, Jie Huang, Jing Du, Huimin Gan, Lu Qiu, Zhu Li, Hongzhong Ren, Guosheng Wei, Yuxian |
author_facet | Liu, Jiazhou Wang, Xiaoyu Sun, Jiazheng Chen, Yuru Li, Jie Huang, Jing Du, Huimin Gan, Lu Qiu, Zhu Li, Hongzhong Ren, Guosheng Wei, Yuxian |
author_sort | Liu, Jiazhou |
collection | PubMed |
description | Breast cancer (BC) is the most common tumor in women, and the molecular mechanism underlying its pathogenesis remains unclear. In this study, we aimed to investigate gene modules related to the phenotypes of BC, and identify representative candidate biomarkers for clinical prognosis of BC patients. Using weighted gene co-expression network analysis, we here identified NPY5R as a hub gene in BC. We further found that NPY5R was frequently downregulated in BC tissues compared with adjacent tumor-matched control tissues, due to its aberrant promoter CpG methylation which was confirmed by methylation analysis and treatment with demethylation agent. Higher expression of NPY5R was closely associated with better prognosis for BC patients. Gene set enrichment analysis showed that transcriptome signatures concerning apoptosis and cell cycle were critically enriched in specimens with elevated NPY5R. Ectopic expression of NPY5R significantly curbed breast tumor cell growth, induced cell apoptosis and G2/M arrest. Moreover, NPY5R also promoted the sensitivity of BC cells to doxorubicin. Mechanistically, we found that NPY5R restricted STAT3 signaling pathway activation through interacting with IL6, which may be responsible for the antitumor activity of NPY5R. Collectively, our findings indicate that NPY5R functions as a tumor suppressor but was frequently downregulated in BC. |
format | Online Article Text |
id | pubmed-8787223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87872232022-01-26 The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy Liu, Jiazhou Wang, Xiaoyu Sun, Jiazheng Chen, Yuru Li, Jie Huang, Jing Du, Huimin Gan, Lu Qiu, Zhu Li, Hongzhong Ren, Guosheng Wei, Yuxian Front Cell Dev Biol Cell and Developmental Biology Breast cancer (BC) is the most common tumor in women, and the molecular mechanism underlying its pathogenesis remains unclear. In this study, we aimed to investigate gene modules related to the phenotypes of BC, and identify representative candidate biomarkers for clinical prognosis of BC patients. Using weighted gene co-expression network analysis, we here identified NPY5R as a hub gene in BC. We further found that NPY5R was frequently downregulated in BC tissues compared with adjacent tumor-matched control tissues, due to its aberrant promoter CpG methylation which was confirmed by methylation analysis and treatment with demethylation agent. Higher expression of NPY5R was closely associated with better prognosis for BC patients. Gene set enrichment analysis showed that transcriptome signatures concerning apoptosis and cell cycle were critically enriched in specimens with elevated NPY5R. Ectopic expression of NPY5R significantly curbed breast tumor cell growth, induced cell apoptosis and G2/M arrest. Moreover, NPY5R also promoted the sensitivity of BC cells to doxorubicin. Mechanistically, we found that NPY5R restricted STAT3 signaling pathway activation through interacting with IL6, which may be responsible for the antitumor activity of NPY5R. Collectively, our findings indicate that NPY5R functions as a tumor suppressor but was frequently downregulated in BC. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787223/ /pubmed/35087836 http://dx.doi.org/10.3389/fcell.2021.798221 Text en Copyright © 2022 Liu, Wang, Sun, Chen, Li, Huang, Du, Gan, Qiu, Li, Ren and Wei. 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 Liu, Jiazhou Wang, Xiaoyu Sun, Jiazheng Chen, Yuru Li, Jie Huang, Jing Du, Huimin Gan, Lu Qiu, Zhu Li, Hongzhong Ren, Guosheng Wei, Yuxian The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title | The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title_full | The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title_fullStr | The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title_full_unstemmed | The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title_short | The Novel Methylation Biomarker NPY5R Sensitizes Breast Cancer Cells to Chemotherapy |
title_sort | novel methylation biomarker npy5r sensitizes breast cancer cells to chemotherapy |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787223/ https://www.ncbi.nlm.nih.gov/pubmed/35087836 http://dx.doi.org/10.3389/fcell.2021.798221 |
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