Department of Obstetrics and Gynaecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
Department of General Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, China.
J Assist Reprod Genet. 2022 Oct;39(10):2381-2393. doi: 10.1007/s10815-022-02593-y. Epub 2022 Sep 7.
To investigate the effects of long intergenic non-protein coding RNA 221 (LINC00221) on preeclampsia (PE) and its mechanism.
The expression of LINC00221 was detected in placental tissues from PE patients and normal pregnant women (non-PE). Next, the effects of LINC00221 silencing on trophoblast cells (HTR-8/SVneo and JEG-3) and co-cultured HUVECs or macrophages were evaluated. Afterwards, miR-542-3p was confirmed to bind to LINC00221 directly, and miR-542-3p mimics and inhibitors were transfected into trophoblast cells. Next, a rescue experiment was performed to examine the effect of LINC00221/miR-542-3p axis. Finally, the effect of LINC00221 was also verified in vivo in rat PE models.
The expression of LINC00221 was higher in placental tissues of PE patients than those of non-PE. LINC00221 silencing significantly reduced MCP1 level and increased the VEGF level in trophoblast cells. LINC00221 knockdown in trophoblast cells remarkably enhanced VEGFR expression and the angiopoiesis of HUVECs, and decreased the migration and invasion of macrophages and reduced TNF-α level. Besides, LINC00221 knockdown decreased CHOP, p-IREα, p-PERK, and iNOS expression and increased Trx expression. Notably, LINC00221 negatively regulated miR-542-3p expression. MiR-542-3p overexpression had an effect to that of LINC00221 knockdown, while miR-542-3p inhibition had the opposite effect. Treatment with miR-542-3p inhibitors partially reversed the protective effect of LINC00221 silencing. PE rat model results were consistent with those of in vitro experiments.
Downregulation of LINC00221 might reduce dysfunction, inflammatory responses, endoplasmic reticulum stress, and oxidative stress, and thereby protect against PE by augmenting miR-542-3p.
探讨长链非编码 RNA 221（LINC00221）对先兆子痫（PE）的影响及其机制。
检测 PE 患者和正常孕妇（非-PE）胎盘组织中 LINC00221 的表达。然后，评估 LINC00221 沉默对滋养细胞（HTR-8/SVneo 和 JEG-3）和共培养的 HUVEC 或巨噬细胞的影响。随后，证实 miR-542-3p 可直接与 LINC00221 结合，并转染 miR-542-3p 模拟物和抑制剂进入滋养细胞。接下来，进行挽救实验以检查 LINC00221/miR-542-3p 轴的作用。最后，在大鼠 PE 模型中也验证了 LINC00221 的作用。
PE 患者胎盘组织中 LINC00221 的表达高于非-PE。LINC00221 沉默显著降低了滋养细胞中 MCP1 水平，增加了 VEGF 水平。LINC00221 敲低可显著增强 VEGFR 的表达和 HUVEC 的血管生成，减少巨噬细胞的迁移和侵袭，并降低 TNF-α 水平。此外，LINC00221 敲低可降低 CHOP、p-IREα、p-PERK 和 iNOS 的表达，增加 Trx 的表达。值得注意的是，LINC00221 负调控 miR-542-3p 的表达。miR-542-3p 的过表达具有 LINC00221 敲低的作用，而 miR-542-3p 的抑制则具有相反的作用。用 miR-542-3p 抑制剂处理可部分逆转 LINC00221 沉默的保护作用。PE 大鼠模型的结果与体外实验结果一致。
下调 LINC00221 可能通过增强 miR-542-3p 减少功能障碍、炎症反应、内质网应激和氧化应激，从而预防 PE。
