Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 2018 May 5;499(2):314-320. doi: 10.1016/j.bbrc.2018.03.154. Epub 2018 Mar 26.
Malate Dehydrogenase (MDH) 1 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'UTR region of MDH1. These analyses revealed that mir-126-5p has three binding sites in the 3'UTR 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.
苹果酸脱氢酶 1（MDH1）最近被证实其在非小细胞肺癌（NSCLCs）中高表达，并具有预后价值。然而，目前尚不清楚 MDH1 的表达是如何调控的，也没有针对 MDH1 的当前分子或化学靶向策略。这可能是由于其同工酶苹果酸脱氢酶 2（MDH2）在结构和酶学上的相似性所致。然而，MDH1 和 MDH2 由不同的基因编码，这为在表达水平上进行调节提供了可能性。在这里，我们通过计算机筛选出特异性靶向 MDH1 的 3'UTR 区域的 microRNAs（miRs）。这些分析表明，miR-126-5p 在 MDH1 的 3'UTR 区域有三个结合位点。此外，我们还发现 miR-126-5p 的表达抑制了 MDH1 的酶活性、线粒体呼吸并导致 NSCLC 细胞系的细胞死亡。
