Department of Animal Physiology and Developmental Biology, Institute of Experimental Biology, Adam Mickiewicz University in Poznań, Poznań, Poland; NanoBioMedical Centre, Adam Mickiewicz University in Poznań, Poznań, Poland.
Chair and Department of Cell Biology, Poznan University of Medical Sciences, Poznań, Poland.
Exp Mol Pathol. 2020 Dec;117:104530. doi: 10.1016/j.yexmp.2020.104530. Epub 2020 Sep 12.
It is well known that mitochondrial dysfunctions are involved in tumorigenesis. A special interest of scientists is mitochondrial ND1 gene (mtND1). Recently detected mutations in the mtND1 can disrupt the normal activity of complex I and affect oxidative phosphorylation, thus leading to increase reactive oxygen species production. This study was undertaken to determine the alternations in the mtND1 and evaluate their association with development of precancerous lesions and cervical cancer.
In the study 29 cervical cancer, 28 low grade squamous intraepithelial lesion (L-SIL) and 30 high grade squamous intraepithelial lesion (H-SIL) HPV positive fragments tissue were screened for the presence of mtND1 mutations.
Our study showed that mutations in the mtND1 gene were detected in patients with precancerous stage, as well as cervical cancer. We have identified 12 point mutations in 116 analyzed precancerous and cancer samples HPV positive. Most detected missense mutations were previously described, except one (p. M156K) with Grantham value 95. The lower expression of mRNA ND1 was detected in cervical cancer cases and in all samples in which mtND1 mutations were identified. Our analyses revealed that level of ROS production was higher in cervical cancer tissues and all cases characterized by mtND1 mutations.
We hypothesize that mutations in MT-ND1 observed in H-SIL and cancer could activate cervical carcinogenesis by increased ROS production.
众所周知，线粒体功能障碍与肿瘤发生有关。科学家特别关注线粒体 ND1 基因（mtND1）。最近在 mtND1 中检测到的突变可以破坏复合物 I 的正常活性并影响氧化磷酸化，从而导致活性氧（ROS）产生增加。本研究旨在确定 mtND1 的改变，并评估其与癌前病变和宫颈癌的发展的关系。
在这项研究中，对 29 例宫颈癌、28 例低级别鳞状上皮内病变（L-SIL）和 30 例高级别鳞状上皮内病变（H-SIL）HPV 阳性组织片段进行了 mtND1 突变筛查。
我们的研究表明，癌前病变和宫颈癌患者的 mtND1 基因发生了突变。我们在 116 例分析的 HPV 阳性癌前和癌症样本中发现了 12 个点突变。除了一个（p.M156K）具有 95 的 Grantham 值外，大多数检测到的错义突变之前已有描述。在宫颈癌病例和所有鉴定出 mtND1 突变的样本中，检测到 ND1 mRNA 的表达降低。我们的分析表明，宫颈癌组织和所有具有 mtND1 突变的病例中 ROS 产生水平较高。
我们假设在 H-SIL 和癌症中观察到的 MT-ND1 突变可能通过增加 ROS 产生激活宫颈癌的发生。
