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

doi:10.1016/j.toxlet.2015.05.019

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/18186

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/18186

Title:	Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression
Authors:	Chiou, Y.-H.;Liou, S.-H.;Wong, R.-H.;Chen, Chen C.-Y.;Lee, H.
Keywords:	EGFR mutation;MiR-21;Nickel;NSCLC;RECK
Date:	2015
Issue Date:	2017-08-08T09:49:15Z (UTC)
Publisher:	Elsevier Ireland Ltd
ISSN:	3784274
Abstract:	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. © 2015 Elsevier Ireland Ltd.
URI:	http://dx.doi.org/10.1016/j.toxlet.2015.05.019 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930641697&doi=10.1016%2fj.toxlet.2015.05.019&partnerID=40&md5=cb5ebe01da1a8c63e9cad7e25107b307 https://ir.csmu.edu.tw:8080/ir/handle/310902500/18186
Relation:	Toxicology Letters 237(1) ,46-54
Appears in Collections:	[醫學系] 期刊論文

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