Department of Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, Jiangsu Province, China.
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
J Cell Physiol. 2020 Oct;235(10):7410-7419. doi: 10.1002/jcp.29643. Epub 2020 Feb 17.
Numerous studies have suggested that urothelial cancer-associated 1 (UCA1) acts as a suppressor gene affecting cell proliferation and migration. However, the biological role and the potential mechanism of UCA1 in the progression of pre-eclampsia (PE) remains unclear. The UCA1 level was markedly upregulated in PE pregnancies relative to non-PE ones in GSE75010 and tissues. A higher body mass index (BMI), maximum systolic blood pressure (BP), and maximum diastolic BP were observed in PE pregnancies, whereas the newborn weight z-score was lower compared with those of non-PE pregnancies. Knockdown of UCA1 accelerated the proliferative migratory abilities and cell cycle progression, but inhibited apoptosis of HTR-8/SVneo and JAR cells. Then, we found that Janus kinases 2 (JAK2) was negatively correlated with UCA1. In addition, JAK2 was downregulated in the placenta of PE pregnancies and was negatively regulated by UCA1. UCA1 was mainly enriched in the nucleus. Knockdown of UCA1 reduced the occupancies of the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and H3K27me3 on the Janus kinase 2 (JAK2) promoter regions. Finally, rescue experiments found that transfection of short-hairpin JAK2 attenuated proliferative and migratory abilities of trophoblasts, which were partially reversed after UCA1 knockdown. In short, UCA1 is upregulated in the trophocytes of PE pregnancies and accelerates trophoblast cell invasion and proliferation by downregulating JAK2.
大量研究表明，尿路上皮癌相关 1（UCA1）作为一种抑制基因，影响细胞增殖和迁移。然而，UCA1 在子痫前期（PE）进展中的生物学作用和潜在机制尚不清楚。在 GSE75010 和组织中，PE 妊娠中 UCA1 的水平明显上调。PE 妊娠的体重指数（BMI）、最大收缩压（BP）和最大舒张压较高，而新生儿体重 z 评分低于非 PE 妊娠。UCA1 的敲低加速了 HTR-8/SVneo 和 JAR 细胞的增殖迁移能力和细胞周期进程，但抑制了细胞凋亡。然后，我们发现 Janus 激酶 2（JAK2）与 UCA1 呈负相关。此外，PE 妊娠胎盘中的 JAK2 下调，受 UCA1 负调控。UCA1 主要富集在核内。UCA1 的敲低降低了增强子结合锌指蛋白 2 多梳抑制复合物 2 亚基（EZH2）和 H3K27me3 在 Janus 激酶 2（JAK2）启动子区域的占有率。最后，挽救实验发现短发夹 JAK2 的转染降低了滋养细胞的增殖和迁移能力，而 UCA1 敲低后部分逆转。总之，UCA1 在 PE 妊娠的滋养细胞中上调，并通过下调 JAK2 加速滋养细胞的侵袭和增殖。
