Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Dis Markers. 2022 Jun 28;2022:6582357. doi: 10.1155/2022/6582357. eCollection 2022.
The genetic pathogenesis of selective intrauterine growth restriction (sIUGR) remains elusive, with evidence suggesting an important role of epigenetic factors such as microRNAs. In this study, we explored the relevance of miR-373-3p to the occurrence of sIUGR. Hypoxia enhanced the levels of miR-373-3p and hypoxia-inducible factor (HIF)-1, while knockdown not only boosted the migration and proliferation of HTR8 cells but also suppressed the hypoxia-induced upregulation of miR-373-3p and SLC38A1. By contrast, HIF-1 overexpression induced miR-373-3p downregulation and SLC38A1 upregulation, reducing cell growth and migration, which could be reversed by a miR-373-3p inhibitor. Importantly, the miR-373-3p inhibitor and mimic reproduced phenomena similar to those induced by HIF-1 downregulation and overexpression, respectively (including altered SLC38A1 expression, mTOR activation, cell growth, and migration). Mechanistically, the miRNA regulated cell behaviors and related mTOR signaling by targeting SLC38A1 expression through an interaction with the 3'-untranslated region of SLC38A1. The placental tissues of smaller sIUGR fetuses exhibited miR-373-3p and HIF-1 upregulation, SLC38A1 downregulation, and activated mTOR. Overall, miR-373-3p appears to restrict the growth and migration of HTR8 trophoblast cells by targeting SLC38A1, as observed in the placental tissues associated with smaller sIUGR fetuses, and it could have utility in the diagnosis and treatment of this disorder.
选择性宫内生长受限（sIUGR）的遗传发病机制仍不清楚，有证据表明表观遗传因素如 microRNAs 起着重要作用。在这项研究中，我们探讨了 miR-373-3p 与 sIUGR 发生的相关性。低氧增强了 miR-373-3p 和缺氧诱导因子（HIF）-1 的水平，而 knockdown 不仅促进了 HTR8 细胞的迁移和增殖，还抑制了低氧诱导的 miR-373-3p 和 SLC38A1 的上调。相比之下，HIF-1 过表达诱导 miR-373-3p 下调和 SLC38A1 上调，减少细胞生长和迁移，这可以被 miR-373-3p 抑制剂逆转。重要的是，miR-373-3p 抑制剂和模拟物分别再现了类似于 HIF-1 下调和过表达诱导的现象（包括改变 SLC38A1 表达、mTOR 激活、细胞生长和迁移）。从机制上讲，miRNA 通过与 SLC38A1 的 3'非翻译区相互作用来调节细胞行为和相关的 mTOR 信号通路，从而调节细胞行为和相关的 mTOR 信号通路。较小的 sIUGR 胎儿的胎盘组织表现出 miR-373-3p 和 HIF-1 的上调、SLC38A1 的下调和激活的 mTOR。总的来说，miR-373-3p 似乎通过靶向 SLC38A1 来限制 HTR8 滋养细胞的生长和迁移，正如与较小的 sIUGR 胎儿相关的胎盘组织中观察到的那样，它可能在该疾病的诊断和治疗中有应用价值。
