复发性自然流产(RSA)是一个涉及多种因素的复杂病理过程,其中滋养细胞功能失调不容忽视。长非编码RNA(lncRNA)已被报道在调节RSA中滋养细胞的功能中起重要作用。然而,lncRNA小核仁RNA宿主基因12(lncSNHG12)的影响和潜在机制尚不清楚。通过体内实验和临床样品研究了lncSNHG12在RSA中的作用。进行Co-IP和RNA下拉以探索滋养细胞的分子机制。我们的结果表明,lncSNHG12通过与碘甲状腺原氨酸脱碘酶2(Dio2)相互作用促进滋养细胞的迁移和侵袭,通过与蜗牛相互作用调节滋养细胞的EMT过程。此外,体内实验证实lncSNHG12可以提高流产小鼠的胎儿吸收率。临床样本显示lncSNHG12,Dio2和Snail在RSA患者的绒毛组织中下调,lncSNHG12与Dio2以及Dio2与Snail之间呈正相关。总之,lncSNHG12/Dio2/Snail轴可能通过调节滋养细胞的侵袭和迁移参与RSA的发生发展。缩写:RSA,复发性自然流产;EVT,绒毛外滋养层;EMT,上皮-间质转化;lncRNA,长链非编码RNA;Dio2,碘甲状腺原氨酸脱碘酶2;SNHGs,小核RNA宿主基因;snoRNAs,小核细胞RNA;LPS,脂多糖;De,衍生decidua;Jz,连接区;Lz,迷宫区;RIP,RNA结合蛋白免疫沉淀;Co-IP,免疫共沉淀;RPISeq,RNA-蛋白质相互作用预测。
Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with
Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and
Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and
Snail. In summary, the lncSNHG12/Dio2/
Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction.