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The risk variant rs884225 within EGFR impairs miR-103a-3p’s anti-tumourigenic function in non-small cell lung cancer

Authors :
Dong Zhang
Ying Li
Sujie Zhang
Quanbo Ji
Xiaoyan Ma
Qinong Ye
Jinliang Wang
Jing Yang
Shunchang Jiao
Xuelin Zhang
Xiaojie Xu
Xiang Zhu
Xiang Yan
Lei Kang
Yi Hu
Fan Zhongyi
Ying Liu
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.

Details

ISSN :
14765594 and 09509232
Volume :
38
Database :
OpenAIRE
Journal :
Oncogene
Accession number :
edsair.doi.dedup.....8c76c38095a6d4800c2fc9e29c753018