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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....

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Autores principales: Liu, Jiazhou, Wang, Xiaoyu, Sun, Jiazheng, Chen, Yuru, Li, Jie, Huang, Jing, Du, Huimin, Gan, Lu, Qiu, Zhu, Li, Hongzhong, Ren, Guosheng, Wei, Yuxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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