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The risk variant rs884225 within EGFR impairs miR-103a-3p’s anti-tumourigenic function in non-small cell lung cancer
- Source :
- Oncogene. 38:2291-2304
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Epidermal growth factor receptor (EGFR) status is the major determinant of non-small cell lung cancer (NSCLC) therapy selection. Studies have hinted that EGFR antibodies or tyrosine kinase inhibitors were beneficial in patients with EGFR mutation-negative but EGFR-overexpressing of NSCLC. However, the mechanisms underlying EGFR amplification and overexpression in NSCLC remain largely unknown. Here, we report that rs884225, a single nucleotide polymorphism in the EGFR 3'-terminal untranslated region, was significantly associated with EGFR expression level and contributed to NSCLC susceptibility. Mechanistically, the rs884225 C allele enhanced EGFR expression by altering the miR-103a-3p binding site, thus impairing miR-103a-3p's anti-tumourigenic function. As a tumour suppressor gene, miR-103a-3p expression correlated with overall and recurrence-free survival in NSCLC patients. Furthermore, miR-103a-3p inhibited growth and metastasis via effects on the KRAS pathway and epithelial-to-mesenchymal transition in EGFR wild-type NSCLC cell lines, respectively, which substantially reduced EGFR expression and activity. Thus, rs884225 may be a biomarker for NSCLC susceptibility, and miR-103a-3p may be a potential therapeutic target in NSCLC.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Lung Neoplasms
medicine.disease_cause
Polymorphism, Single Nucleotide
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
Risk Factors
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Genetics
medicine
Carcinoma
Animals
Humans
Genetic Predisposition to Disease
Epidermal growth factor receptor
Lung cancer
3' Untranslated Regions
neoplasms
Molecular Biology
Regulation of gene expression
Binding Sites
biology
Three prime untranslated region
medicine.disease
respiratory tract diseases
ErbB Receptors
Gene Expression Regulation, Neoplastic
MicroRNAs
Cell Transformation, Neoplastic
030104 developmental biology
Case-Control Studies
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
KRAS
Tyrosine kinase
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....8c76c38095a6d4800c2fc9e29c753018