Wang Xueqin, Zhang Lu, Guan Chunyi, Dong Yichao, Liu Haining, Ma Xu, Xia Hongfei
Reproductive and Genetic Center of National Research Institute for Family Planning Beijing, China.
Department of Reproductive Medicine, Qingdao Municipal Hospital, Qingdao University Qingdao, Shandong, China.
Am J Transl Res. 2020 May 15;12(5):1928-1941. eCollection 2020.
Rs11614913 in pri- is involved in the occurrence of many diseases, especially in cancers. However, it remains unknown whether is associated with human recurrent spontaneous abortion (RSA) in Chinese Han population. Our study found that rs11614913 T/T in pri- was associated with the increase risk of human unexplained RSA (URSA) in recessive mode in Chinese Han population. The T allele of rs11614913 increased the production of mature . Rs11614913 T/T inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further investigation discovered that dihydrofolate reductase () was the target of and inversely regulated by . Dual-luciferase assay indicated that T allele in rs11614913 could more effectively suppress expression than C allele. In addition, C to T substitution in rs11614913 attenuated the sensibility of cells to mifepristone. Collectively, our data suggest that rs11614913 T/T in pri- may be conductive to the genetic predisposition to RSA by disrupting the production of mature and reinforcing the expression of .
pri- 基因中的 Rs11614913 与多种疾病的发生有关,尤其是癌症。然而,在中国汉族人群中,它是否与人类复发性自然流产(RSA)相关尚不清楚。我们的研究发现,在中国汉族人群中,pri- 基因中的 rs11614913 T/T 以隐性模式与人类不明原因 RSA(URSA)风险增加相关。rs11614913 的 T 等位基因增加了成熟……的产生。rs11614913 T/T 抑制 HTR-8/SVneo 细胞增殖和迁移并促进细胞凋亡。进一步研究发现二氢叶酸还原酶(……)是……的靶标并受……反向调节。双荧光素酶测定表明,rs11614913 中的 T 等位基因比 C 等位基因能更有效地抑制……表达。此外,rs11614913 中 C 到 T 的替换减弱了细胞对米非司酮的敏感性。总体而言,我们的数据表明,pri- 基因中的 rs11614913 T/T 可能通过破坏成熟……的产生并增强……的表达,导致 RSA 的遗传易感性。 (注:原文中部分关键基因或蛋白名称未完整给出,翻译时保留了英文原文)