Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression

Yu Hu Chiou, Saou Hsing Liou, Ruey Hong Wong, Chih Yi Chen, Huei Lee

研究成果: 雜誌貢獻文章

18 引文 (Scopus)

摘要

We recently reported that nickel accumulation in lung tissues may be associated with an increased in p53 mutation risk via reduced DNA repair activity. Here, we hypothesized that nickel accumulation in lung tissues could contribute to EGFR mutations in never-smokers with lung cancer. We enrolled 76 never-smoking patients to evaluate nickel level in adjacent normal lung tissues by ICP-MS. The prevalence of EGFR mutations was significantly higher in the high-nickel subgroup than in the low-nickel subgroup. Intriguingly, the OR for the occurrence of EGFR mutations in female, adenocarcinoma, and female adenocarcinoma patients was higher than that of all patients. Mechanistically, SPRY2 and RECK expressions were decreased by nickel-induced miR-21 via activation of the EGFR/NF-κB signaling pathway, which promoted invasiveness in lung cancer cells, and particularly in the cells with EGFR L858R expression vector transfection. The patients' nickel levels were associated with miR-21 expression levels. Kaplan-Meier analysis revealed poorer overall survival (OS) and shorter relapse free survival (RFS) in the high-nickel subgroup than in low-nickel subgroup. The high-nickel/high-miR-21 subgroup had shorter OS and RFS periods when compared to the low-nickel/low-miR-21 subgroup. Our findings support previous epidemiological studies indicating that nickel exposure may not only contribute to cancer incidence but also promote tumor invasion in lung cancer.
原文英語
頁(從 - 到)46-54
頁數9
期刊Toxicology Letters
237
發行號1
DOIs
出版狀態已發佈 - 八月 9 2015

指紋

Nickel
MicroRNAs
Tumors
Lung Neoplasms
Mutation
Neoplasms
Survival
Tissue
Lung
Adenocarcinoma
Recurrence
Kaplan-Meier Estimate
DNA Repair
Transfection
Epidemiologic Studies
Repair
Smoking
Chemical activation
Cells

ASJC Scopus subject areas

  • Toxicology

引用此文

Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression. / Chiou, Yu Hu; Liou, Saou Hsing; Wong, Ruey Hong; Chen, Chih Yi; Lee, Huei.

於: Toxicology Letters, 卷 237, 編號 1, 09.08.2015, p. 46-54.

研究成果: 雜誌貢獻文章

Chiou, Yu Hu ; Liou, Saou Hsing ; Wong, Ruey Hong ; Chen, Chih Yi ; Lee, Huei. / Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression. 於: Toxicology Letters. 2015 ; 卷 237, 編號 1. 頁 46-54.
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