Malate Dehydrogenase (MDH) I has recently been shown to be highly expressed and display prognostic value in non-small cell lung carcinomas (NSCLCs). However, it is not known how MDH1 expression is regulated and there is no current molecular or chemical strategy that specifically targets MDH1. This may be due to structural and enzymatic similarities with its isoenzyme, malate dehydrogenase 2 (MDH2). However, MDH1 and MDH2 are encoded by distinct genes and this opens up the possibility for modulation at the expression level. Here, we screened in silico for microRNAs (miRs) that selectively targets the 3'IJTR region of MDH1. These analyses revealed that mir-126-5p has three binding sites in the 3'IJTR region of MDH1. Additionally, we show that expression of miR-126-5p suppresses the enzymatic activity of MDH1, mitochondrial respiration and caused cell death in NSCLC cell lines. (C) 2018 Elsevier Inc. All rights reserved.