Luo Yong, Zou Yang, Wu Juan, Zhang Zi-Yu, Liu Fa-Ying, Li Li-Ping, Huang Ou-Ping
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Ann Hum Genet. 2019 Jul;83(4):220-230. doi: 10.1111/ahg.12303. Epub 2019 Mar 1.
Uterine fibroids (UFs) are the most common benign neoplasms, but their pathogenesis is not completely understood. Thus far, alterations in the mitochondrial DNA (mtDNA) content and the mtDNA 4977-bp deletion level in UFs, as well as the corresponding nontumorous tissue, have remained elusive. To test whether large mtDNA deletions and mtDNA content are involved in the pathogenesis of UFs, a total of 309 UF tissues and 28 paired adjacent myometrium from 270 UF patients were enrolled for the analysis of large mtDNA deletions and mtDNA content through the use of nested PCR and qPCR techniques, respectively. In our samples, a 4977-bp deletion was identified: 36 out of 309 UF tissues (11.56%) and 15 out of 28 (53.57%) paired adjacent myometrium were detected to harbor the 4977-bp deletion. In addition, a novel 4838-bp mtDNA deletion was identified in three UF tissues, and other different sizes of deleted fragments (4910, 4926, 5135-bp) were also found in UFs for the first time. Furthermore, older age was significantly associated with an mtDNA large deletion in the paired adjacent myometrium. We also found that increased mtDNA content and higher expression of ND1 occurred in solitary fibroids compared to adjacent myometrium. In conclusion, we identified a lower frequency of mtDNA large deletions and some novel large deletion in UFs for the first time. Furthermore, there was a general increase of mtDNA copy number during solitary UF development. Although the definite mechanism by which mtDNA was altered is supposed to be further confirmed, it will be helpful for further studies on the pathological mechanism of UFs.
子宫肌瘤(UFs)是最常见的良性肿瘤,但其发病机制尚未完全明确。迄今为止,子宫肌瘤及其相应的非肿瘤组织中线粒体DNA(mtDNA)含量和mtDNA 4977-bp缺失水平仍不清楚。为了检测大的mtDNA缺失和mtDNA含量是否参与子宫肌瘤的发病机制,我们纳入了270例子宫肌瘤患者的309份子宫肌瘤组织和28对配对的相邻子宫肌层,分别采用巢式PCR和qPCR技术分析大的mtDNA缺失和mtDNA含量。在我们的样本中,检测到了4977-bp缺失:309份子宫肌瘤组织中有36份(11.56%),28对配对的相邻子宫肌层中有15份(53.57%)检测到含有4977-bp缺失。此外,在3份子宫肌瘤组织中鉴定出一种新的4838-bp mtDNA缺失,并且在子宫肌瘤中首次发现了其他不同大小的缺失片段(4910、4926、5135-bp)。此外,年龄较大与配对的相邻子宫肌层中的mtDNA大片段缺失显著相关。我们还发现,与相邻子宫肌层相比,孤立性肌瘤中mtDNA含量增加,且ND1表达更高。总之,我们首次在子宫肌瘤中发现了较低频率的mtDNA大片段缺失和一些新的大片段缺失。此外,在孤立性子宫肌瘤发生过程中mtDNA拷贝数普遍增加。尽管mtDNA改变的确切机制有待进一步证实,但这将有助于进一步研究子宫肌瘤的病理机制。