A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling.
Jing LinRoza ZandiRuping ShaoJian GuYuanqin YeJing WangYang ZhaoAlexander PertsemlidisIgnacio I WistubaXifeng WuJack A RothLin JiPublished in: Scientific reports (2017)
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.
Keyphrases
- genome wide
- cell proliferation
- long non coding rna
- poor prognosis
- long noncoding rna
- dna methylation
- high density
- small cell lung cancer
- end stage renal disease
- early stage
- ejection fraction
- newly diagnosed
- chronic kidney disease
- signaling pathway
- genetic diversity
- advanced non small cell lung cancer
- high throughput
- radiation therapy
- small molecule
- patient reported outcomes
- machine learning
- epidermal growth factor receptor
- binding protein
- single cell
- deep learning
- data analysis