Su Xing, Hu Yi, Li Ying, Cao Jing-Li, Wang Xue-Qin, Ma Xu, Xia Hong-Fei
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
Reproduction. 2015 Jul;150(1):65-76. doi: 10.1530/REP-15-0007. Epub 2015 Apr 29.
Although the relationship between polymorphisms in microRNAs (miRNAs) and recurrent pregnancy loss (RPL) has been studied, there is very little data available in the literature. In the present study, we scanned 55 potentially functional polymorphisms in the miRNA coding region in Chinese women with unexplained RPL (URPL; no. 2011-10). The rs6505162 C>A in the MIR423 coding region was found to be significantly associated with the occurrence of human URPL. The rare A allele contributed to an increase in the expression of mature MIR423. C to A substitution in the polymorphism rs6505162 in pre-MIR423 repressed cell proliferation and migratory capacity. Further investigations showed that MIR423 could inversely regulate the expression of proliferation-associated 2 group 4 (PA2G4) by binding the 3'-UTR of PA2G4. Dual-luciferase assay indicated that the A allele in the polymorphism rs6505162 could more effectively suppress the expression of PA2G4 than the C allele could. Collectively, the present data suggest that rs6505162 C>A in pre-MIR423 may contribute to the genetic predisposition to RPL by disrupting the production of mature MIR423 and its target gene, which consequently interferes with MIR423 functioning.
尽管已经对微小RNA（miRNA）多态性与复发性流产（RPL）之间的关系进行了研究，但文献中可用的数据非常少。在本研究中，我们扫描了中国不明原因复发性流产（URPL；编号2011 - 10）女性miRNA编码区的55个潜在功能性多态性。发现MIR423编码区的rs6505162 C>A与人类URPL的发生显著相关。罕见的A等位基因导致成熟MIR423表达增加。前体MIR423中多态性rs6505162的C到A替换抑制了细胞增殖和迁移能力。进一步研究表明，MIR423可通过结合PA2G4的3'-UTR反向调节增殖相关2组4（PA2G4）的表达。双荧光素酶测定表明，多态性rs6505162中的A等位基因比C等位基因能更有效地抑制PA2G4的表达。总体而言，目前的数据表明，前体MIR423中的rs6505162 C>A可能通过破坏成熟MIR423及其靶基因的产生，从而干扰MIR423的功能，导致RPL的遗传易感性。
