Wang Lie, Chen Zhi-Jun, Zhang Yong-Kui, Le Han-Bo
Department of Cardiothoracic Surgery, Zhou Shan Hospital Zhou Shan, Zhejiang, China.
Int J Clin Exp Med. 2015 Aug 15;8(8):13341-6. eCollection 2015.
Alternations in mitochondrial genome resulting in mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondrial tRNA (mt-tRNA) is known for its high frequencies of polymorphisms and mutations, however, the roles of these mutations and polymorphisms in lung cancer are among heated debates. To evaluate the possible roles of reported mt-tRNA mutations in lung cancer, we examine recent published paper concerning three mt-tRNA mutations with lung cancer: A7460G in tRNA(Ser (UCN)) gene, G5563A in tRNA(Trp) gene and A12172G in tRNA(His) gene. We perform the phylogenetic approach to investigate the deleterious roles of these mutations in lung cancer, moreover, we use bioinformatics tool to predict the secondary structure of mt-tRNAs with and without these mutations. In addition, through the application of pathogenicity scoring system, we find that only the A12172G mutation is regarded as a pathogenic mutation, whereas other mutations may act as neutral polymorphisms in human population. Thus, our study provides the novel insight into the molecular pathogenesis of mt-tRNA mutations in lung cancer.
长期以来，人们一直假设线粒体基因组的改变导致线粒体功能障碍与肿瘤发生有关。线粒体转运RNA（mt-tRNA）以其多态性和突变的高频率而闻名，然而，这些突变和多态性在肺癌中的作用一直是激烈争论的焦点。为了评估已报道的mt-tRNA突变在肺癌中的可能作用，我们研究了最近发表的关于三种与肺癌相关的mt-tRNA突变的论文：tRNA（Ser（UCN））基因中的A7460G、tRNA（Trp）基因中的G5563A和tRNA（His）基因中的A12172G。我们采用系统发育方法来研究这些突变在肺癌中的有害作用，此外，我们使用生物信息学工具来预测有或没有这些突变的mt-tRNA的二级结构。此外，通过应用致病性评分系统，我们发现只有A12172G突变被认为是致病性突变，而其他突变在人群中可能作为中性多态性存在。因此，我们的研究为肺癌中mt-tRNA突变的分子发病机制提供了新的见解。
