Abstract:
:Mutation in isocitrate dehydrogenase (IDH) leads to an aberrant function of the enzyme, leading to the production of hydroxyglutarate, as well as changes in cellular metabolism, DNA methylation and histone modification. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). However, the contribution of IDH1 mutation in the malignant transformation and development of NSCLC is unclear. In our study, we show that IDH1 R132H enhanced the migration and proliferation of NSCLC cells. Moreover, IDH1 R132H was a crucial modulator of 2-hydroxyglutarate, whose production from cells with IDH1 mutation promoted the binding of DNA-methyltransferase 1 (DNMT1) to the Fibulin-5 promoter, leading to its methylation. As a result, Fibulin-5 silencing in cells with IDH1 mutation enhanced the migration and proliferation of NSCLC cells. We show that the IDH1 mutation was present in tissues sampled from patients with NSCLC, which was reversely linked to Fibulin-5 expression. In this study, we suggest an innovative model for IDH1 R132H/Fibulin-5 pathway, which could throw light upon the activity of IDH1 R132H in NSCLC.
journal_name
Open Bioljournal_title
Open biologyauthors
Yan B,Hu Y,Ma T,Wang Ydoi
10.1098/rsob.180086subject
Has Abstractpub_date
2018-10-10 00:00:00issue
10issn
2046-2441pii
rsob.180086journal_volume
8pub_type
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