Mpo promoter polymorphism rs2333227 enhances malignant phenotypes of colorectal cancer by altering the binding affinity of AP-2a

Qingtao Meng, Shenshen Wu, Yajie Wang, Jin Xu, Hao Sun, Runze Lu, Na Gao, Hongbao Yang, Xiaobo Li, Boping Tang, Michael Aschner, Rui Chen

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2 Citations (Scopus)

Abstract

Myeloperoxidase (MPO) promoter SNPs rs2243828 (764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo. Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2a to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A–MMP9 axis–mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of colorectal cancer. Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer.

Original languageEnglish (US)
Pages (from-to)2760-2769
Number of pages10
JournalCancer Research
Volume78
Issue number10
DOIs
StatePublished - May 15 2018

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Peroxidase
Colorectal Neoplasms
Phenotype
Single Nucleotide Polymorphism
Genotype
Mutation
Survival
Transcription Factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mpo promoter polymorphism rs2333227 enhances malignant phenotypes of colorectal cancer by altering the binding affinity of AP-2a. / Meng, Qingtao; Wu, Shenshen; Wang, Yajie; Xu, Jin; Sun, Hao; Lu, Runze; Gao, Na; Yang, Hongbao; Li, Xiaobo; Tang, Boping; Aschner, Michael; Chen, Rui.

In: Cancer Research, Vol. 78, No. 10, 15.05.2018, p. 2760-2769.

Research output: Contribution to journalArticle

Meng, Qingtao ; Wu, Shenshen ; Wang, Yajie ; Xu, Jin ; Sun, Hao ; Lu, Runze ; Gao, Na ; Yang, Hongbao ; Li, Xiaobo ; Tang, Boping ; Aschner, Michael ; Chen, Rui. / Mpo promoter polymorphism rs2333227 enhances malignant phenotypes of colorectal cancer by altering the binding affinity of AP-2a. In: Cancer Research. 2018 ; Vol. 78, No. 10. pp. 2760-2769.
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abstract = "Myeloperoxidase (MPO) promoter SNPs rs2243828 (764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo. Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2a to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A–MMP9 axis–mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of colorectal cancer. Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer.",
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AU - Meng, Qingtao

AU - Wu, Shenshen

AU - Wang, Yajie

AU - Xu, Jin

AU - Sun, Hao

AU - Lu, Runze

AU - Gao, Na

AU - Yang, Hongbao

AU - Li, Xiaobo

AU - Tang, Boping

AU - Aschner, Michael

AU - Chen, Rui

PY - 2018/5/15

Y1 - 2018/5/15

N2 - Myeloperoxidase (MPO) promoter SNPs rs2243828 (764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo. Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2a to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A–MMP9 axis–mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of colorectal cancer. Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer.

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