Department of Reproductive Health, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, Guangdong, China.
Department of Pathology, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, Guangdong, China.
Biol Reprod. 2024 Jul 12;111(1):135-147. doi: 10.1093/biolre/ioae030.
This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA contributes to the pathogenesis of unexplained recurrent spontaneous abortion.
Real-time quantitative PCR was employed to assess the differential expression levels of HOX transcript antisense intergenic RNA in chorionic villi tissues from unexplained recurrent spontaneous abortion patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOX transcript antisense intergenic RNA in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8, scratch, and Transwell assays, respectively. The interaction among the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells.
We found that HOX transcript antisense intergenic RNA was downregulated in chorionic villi tissues from unexplained recurrent spontaneous abortion patients. Overexpression of HOX transcript antisense intergenic RNA significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOX transcript antisense intergenic RNA had the opposite effects. We further confirmed the regulatory effect of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis in unexplained recurrent spontaneous abortion. Specifically, HOX transcript antisense intergenic RNA and fibrillin 2 were found to reduce the risk of unexplained recurrent spontaneous abortion by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects.
HOX transcript antisense intergenic RNA promotes unexplained recurrent spontaneous abortion development by targeting inhibition of miR-1277-5p/fibrillin 2 axis.
本研究旨在探讨 HOX 转录物反义基因间 RNA （HOX transcript antisense intergenic RNA，HOTAIR）导致不明原因复发性自然流产发病机制的具体途径。
采用实时定量 PCR 检测不明原因复发性自然流产患者和自愿终止妊娠的孕妇绒毛组织中 HOTAIR 的差异表达。以 HTR-8/SVneo 细胞作为细胞模型。通过 siRNA 转染和 pcDNA3.1 转染分别实现 HOTAIR 的敲低和过表达。采用细胞计数试剂盒-8（cell counting kit-8，CCK-8）、划痕和 Transwell 实验分别评估细胞活力、迁移和侵袭。通过生物信息学分析预测 HOTAIR/miR-1277-5p/纤维连接蛋白 2（fibrillin 2）轴之间的相互作用，并通过体外实验进行验证。进一步在 HTR-8/SVneo 细胞中验证 HOTAIR/miR-1277-5p/纤维连接蛋白 2 信号轴对细胞行为的调节作用。
我们发现 HOTAIR 在不明原因复发性自然流产患者的绒毛组织中表达下调。过表达 HOTAIR 显著增强了 HTR-8/SVneo 细胞的活力、迁移和侵袭能力，而敲低 HOTAIR 则产生相反的效果。我们进一步证实了 HOTAIR/miR-1277-5p/纤维连接蛋白 2 信号轴在不明原因复发性自然流产中的调节作用。具体而言，HOTAIR 和纤维连接蛋白 2 通过增强细胞活力、迁移和侵袭来降低不明原因复发性自然流产的风险，而 miR-1277-5p 则产生相反的作用。
HOTAIR 通过靶向抑制 miR-1277-5p/纤维连接蛋白 2 轴促进不明原因复发性自然流产的发生。
