Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers

Jiefeng Ding, Mei Ling Kuo, Leila Su, Lijun Xue, Frank Luh, Hang Zhang, Jianghai Wang, Tiffany G. Lin, Keqiang Zhang, Peiguo Chu, Shu Zheng, Xiyong Liu, Yun Yen

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ERpositive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.
原文英語
文章編號bgx022
頁(從 - 到)519-531
頁數13
期刊Carcinogenesis
38
發行號5
DOIs
出版狀態已發佈 - 五月 1 2017

指紋

Breast Neoplasms
Survival
Estrogen Receptors
Messenger RNA
Pyrroline Carboxylate Reductases
delta-1-pyrroline-5-carboxylate reductase
Proline
Doxorubicin
Small Interfering RNA
Oxidation-Reduction
Proteins
Biomarkers
Immunohistochemistry
Outcome Assessment (Health Care)
Amino Acids
Drug Therapy
Cell Line
Enzymes
Therapeutics
Growth

ASJC Scopus subject areas

  • Cancer Research

引用此文

Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers. / Ding, Jiefeng; Kuo, Mei Ling; Su, Leila; Xue, Lijun; Luh, Frank; Zhang, Hang; Wang, Jianghai; Lin, Tiffany G.; Zhang, Keqiang; Chu, Peiguo; Zheng, Shu; Liu, Xiyong; Yen, Yun.

於: Carcinogenesis, 卷 38, 編號 5, bgx022, 01.05.2017, p. 519-531.

研究成果: 雜誌貢獻文章

Ding, J, Kuo, ML, Su, L, Xue, L, Luh, F, Zhang, H, Wang, J, Lin, TG, Zhang, K, Chu, P, Zheng, S, Liu, X & Yen, Y 2017, 'Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers', Carcinogenesis, 卷 38, 編號 5, bgx022, 頁 519-531. https://doi.org/10.1093/carcin/bgx022
Ding, Jiefeng ; Kuo, Mei Ling ; Su, Leila ; Xue, Lijun ; Luh, Frank ; Zhang, Hang ; Wang, Jianghai ; Lin, Tiffany G. ; Zhang, Keqiang ; Chu, Peiguo ; Zheng, Shu ; Liu, Xiyong ; Yen, Yun. / Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers. 於: Carcinogenesis. 2017 ; 卷 38, 編號 5. 頁 519-531.
@article{8408e29bbcac4cd1bdaebc36ae8349e3,
title = "Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers",
abstract = "Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ERpositive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.",
author = "Jiefeng Ding and Kuo, {Mei Ling} and Leila Su and Lijun Xue and Frank Luh and Hang Zhang and Jianghai Wang and Lin, {Tiffany G.} and Keqiang Zhang and Peiguo Chu and Shu Zheng and Xiyong Liu and Yun Yen",
year = "2017",
month = "5",
day = "1",
doi = "10.1093/carcin/bgx022",
language = "English",
volume = "38",
pages = "519--531",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers

AU - Ding, Jiefeng

AU - Kuo, Mei Ling

AU - Su, Leila

AU - Xue, Lijun

AU - Luh, Frank

AU - Zhang, Hang

AU - Wang, Jianghai

AU - Lin, Tiffany G.

AU - Zhang, Keqiang

AU - Chu, Peiguo

AU - Zheng, Shu

AU - Liu, Xiyong

AU - Yen, Yun

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ERpositive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.

AB - Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ERpositive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.

UR - http://www.scopus.com/inward/record.url?scp=85019656368&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019656368&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgx022

DO - 10.1093/carcin/bgx022

M3 - Article

VL - 38

SP - 519

EP - 531

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 5

M1 - bgx022

ER -