Scientific Reports: 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 the 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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Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

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