A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling

Jing Lin; Roza Zandi; Ruping Shao; Jian Gu; Yuanqin Ye; Jing Wang; Yang Zhao; Alexander Pertsemlidis; Ignacio I. Wistuba; Xifeng Wu; Jack A. Roth; Lin Ji

doi:10.1038/s41598-017-09604-4

A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling

Jing Lin, Roza Zandi, Ruping Shao, Jian Gu, Yuanqin Ye, Jing Wang, Yang Zhao, Alexander Pertsemlidis, Ignacio I. Wistuba, Xifeng Wu, Jack A. Roth, Lin Ji

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21 Scopus citations

Abstract

Through a new hypothesis-driven and microRNA-pathway-based SNP (miR-SNP) association study we identified a novel miR-SNP (rs713065) in the 3′UTR region of FZD4 gene linked with decreased risk of death in early stage NSCLC patients. We determined biological function and mechanism of action of this FZD4-miR-SNP biomarker in a cellular platform. Our data suggest that FZD4-miR-SNP loci may significantly influence overall survival in NSCLC patients by specifically interacting with miR-204 and modulating FZD4 expression and cellular function in the Wnt-signaling-driven tumor progression. Our findings are bridging the gap between the discovery of epidemiological SNP biomarkers and their biological function and will enable us to develop novel therapeutic strategies that specifically target epigenetic markers in the oncogenic Wnt/FZD signaling pathways in NSCLC.

Original language	English (US)
Article number	9029
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-09604-4
State	Published - Dec 1 2017

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title = "A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling",

abstract = "Through a new hypothesis-driven and microRNA-pathway-based SNP (miR-SNP) association study we identified a novel miR-SNP (rs713065) in the 3′UTR region of FZD4 gene linked with decreased risk of death in early stage NSCLC patients. We determined biological function and mechanism of action of this FZD4-miR-SNP biomarker in a cellular platform. Our data suggest that FZD4-miR-SNP loci may significantly influence overall survival in NSCLC patients by specifically interacting with miR-204 and modulating FZD4 expression and cellular function in the Wnt-signaling-driven tumor progression. Our findings are bridging the gap between the discovery of epidemiological SNP biomarkers and their biological function and will enable us to develop novel therapeutic strategies that specifically target epigenetic markers in the oncogenic Wnt/FZD signaling pathways in NSCLC.",

author = "Jing Lin and Roza Zandi and Ruping Shao and Jian Gu and Yuanqin Ye and Jing Wang and Yang Zhao and Alexander Pertsemlidis and Wistuba, {Ignacio I.} and Xifeng Wu and Roth, {Jack A.} and Lin Ji",

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doi = "10.1038/s41598-017-09604-4",

language = "English (US)",

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T1 - A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling

AU - Lin, Jing

AU - Zandi, Roza

AU - Shao, Ruping

AU - Gu, Jian

AU - Ye, Yuanqin

AU - Wang, Jing

AU - Zhao, Yang

AU - Pertsemlidis, Alexander

AU - Wistuba, Ignacio I.

AU - Wu, Xifeng

AU - Roth, Jack A.

AU - Ji, Lin

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Through a new hypothesis-driven and microRNA-pathway-based SNP (miR-SNP) association study we identified a novel miR-SNP (rs713065) in the 3′UTR region of FZD4 gene linked with decreased risk of death in early stage NSCLC patients. We determined biological function and mechanism of action of this FZD4-miR-SNP biomarker in a cellular platform. Our data suggest that FZD4-miR-SNP loci may significantly influence overall survival in NSCLC patients by specifically interacting with miR-204 and modulating FZD4 expression and cellular function in the Wnt-signaling-driven tumor progression. Our findings are bridging the gap between the discovery of epidemiological SNP biomarkers and their biological function and will enable us to develop novel therapeutic strategies that specifically target epigenetic markers in the oncogenic Wnt/FZD signaling pathways in NSCLC.

AB - Through a new hypothesis-driven and microRNA-pathway-based SNP (miR-SNP) association study we identified a novel miR-SNP (rs713065) in the 3′UTR region of FZD4 gene linked with decreased risk of death in early stage NSCLC patients. We determined biological function and mechanism of action of this FZD4-miR-SNP biomarker in a cellular platform. Our data suggest that FZD4-miR-SNP loci may significantly influence overall survival in NSCLC patients by specifically interacting with miR-204 and modulating FZD4 expression and cellular function in the Wnt-signaling-driven tumor progression. Our findings are bridging the gap between the discovery of epidemiological SNP biomarkers and their biological function and will enable us to develop novel therapeutic strategies that specifically target epigenetic markers in the oncogenic Wnt/FZD signaling pathways in NSCLC.

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A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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