Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China; Reproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China; Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Biochem Pharmacol. 2024 Nov;229:116459. doi: 10.1016/j.bcp.2024.116459. Epub 2024 Aug 3.
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.
复发性自然流产（RSA）是一种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。长链非编码 RNA（lncRNA）已被报道在调节 RSA 中滋养细胞的功能方面发挥重要作用。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本研究了 lncSNHG12 在 RSA 中的作用。通过共免疫沉淀和 RNA 下拉实验探索了滋养细胞中的分子机制。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 SNAI2 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，RSA 患者绒毛组织中 lncSNHG12、Dio2 和 SNAI2 下调，lncSNHG12 与 Dio2 以及 Dio2 与 SNAI2 之间存在正相关关系。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。缩写词：RSA，复发性自然流产；EVTs，绒毛外滋养细胞；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，小核仁 RNA；LPS，脂多糖；De，衍生蜕膜；Jz，连接区；Lz，迷路区；RIP，RNA 结合蛋白免疫沉淀；Co-IP，共免疫沉淀；RPISeq，RNA-蛋白相互作用预测。
