Expression Profile Analysis of Zinc Transporters (ZIP4, ZIP9, ZIP11, ZnT9) in Gliomas and their Correlation with IDH1 Mutation Status.
BACKGROUND
Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status.


METHODS
IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated.


RESULTS
Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However, only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1 displayed higher ZIP11 expression than those without IDH1 mutations.


CONCLUSIONS
This finding indicated that zinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathways or genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4 and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailed biological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1 mutation in gliomagenesis should be further investigated.
School of Life Sciences, Northwest University, Xi'an, China E-mail : whj@nwu.edu.cn, cchen898@nwu.edu.cn.
Xing
X
Kang
Rong
R
Chen
Jie
J
Zhang
Gang
G
Li
Peng-Gao
PG
Dai
Chao
C
Chen
Hui-Juan
HJ
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008527:Medulloblastoma / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors; D055815:Young Adult
D027682:Cation Transport Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C120900:SLC30A9 protein, human; C000604569:SLC39A11 protein, human; C486791:SLC39A4 protein, human; C543108:Slc39a9 protein, human; D014157:Transcription Factors; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human